A new therapeutic approach against COVID-19 Pneumonia – Institute for Ethics and Emerging Technologies

The novel coronavirus disease 2019 (COVID-19) has grown to become a global public health emergency. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases. A new study offers a promising pathway for developing such a treatment.

The new approach involves intravenous transplantation of mesenchymal stem cells (MSCs) into the patients. It was successfully tested in 7 COVID-19 patients, in Beijing YouAn Hospital, Capital Medical University, China. The results are published in the scientific journal Aging and Disease, entitled "Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia".

http://www.aginganddisease.org/article/0000/2152-5250/ad-0-0-216.shtml

The study was conducted by a team led by Dr. Robert Chunhua Zhao, with Shanghai University and Chinese Academy of Medical Sciences & Peking Union Medical College, China.

Moreover the study was reviewed by a scientific committee of the International Society on Aging and Disease (ISOAD) and the recently established UNESCO-affiliated committee on Anti-Aging and Disease Prevention http://www.aginganddisease.org/article/2020/2152-5250/ad-11-1-212.shtml

Based on the 14 days observation, MSCs could cure or significantly improve the functional outcomes of all the seven tested patients without observed adverse effects, contrary to 3 controls. The pulmonary function and symptoms of these seven patients were significantly improved after MSC transplantation. Among them, one severe and two common patients recovered and were discharged in 10 days after the treatment. The improvement was particularly dramatic for an elderly (65 y.o.) male patient in severe critical condition. All of his primary and secondary outcomes improved: the inflammation status, the oxygen saturation, and the functional biochemical indicators returned to normal reference values in 2~4 days after the treatment.

The presented evidence suggests that the therapeutic effects are based on the immunomodulatory capacity of mesenchymal stem cells (restoring the balance of the immune system). The coronavirus infection can stimulate a terrible cytokine storm in the lung, disrupting the balance of cytokines (signaling molecules of the immune system) such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A and TNF cytokines, followed by the edema, dysfunction of the air exchange, acute respiratory distress syndrome, acute cardiac injury and the secondary infection, which may lead to death. The bone-marrow derived MSCs could inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment, thus they could represent a safe and effective treatment for patients with COVID-19 pneumonia, especially for the patients in critically severe conditions. A larger validation study is required and is already underway, yet the initial results are encouraging.

Notably, the coronavirus-infected pneumonia is more likely to affect older individuals, especially older males, with comorbidities, resulting in their severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In other words, aging appears to be the main risk factor for bad outcomes. However, the cure essentially depends on the patient's own immune system. When the overactivated immune system kills the virus, it produces a large number of inflammatory factors, leading to the severe cytokine storms. This suggests that the main reason for the organs damage may be the virus-induced cytokine storm. Older subjects may be much easier to be affected due to immunosenescence. The study showed remarkable recovery of the elderly patients thanks to restoring their immune function.

Thus, the study may have a broader significance, even beyond the treatment of the severe coronavirus disease. This study exemplifies that the general therapeutic improvement of the immune system in the elderly can improve outcome and survival, which may have more general relevance for other aging-related communicable diseases. Thus, this study may inspire and pave the way for further promising directions to investigate the connection between aging and disease, and to treat both communicable and non-communicable aging-related diseases.

The Romanian journalist Laura tefnu spoke with Dr. Ilia Stambler about the broader implications of this research. Ilia Stambler is a co-author in this study who was involved in the study review, interpretation and discussion. He serves as the Outreach Coordinator of the International Society on Aging and Disease (ISOAD) and Director of Research and Development at Shmuel Harofe Geriatric Medical Center in Israel.

Q: How does it feel to be part of the team which discovered a groundbreaking treatment for what is currently considered one of the biggest global challenges?

A: I feel very honored to be included in this extended international team. I hope this team continues its work that will also involve additional collaborations.

Q: As a researcher, what did you find most interesting about this novel coronavirus? What seems most threatening about this new virus?

A: The spreading ability of this virus is relatively high and it has the capacity to affect the entire global population. This is what makes this virus a particularly strong concern for global public health. The social effects of this epidemic are also of great importance. In a sense, this virus is testing the strength of our public health systems. Will the immunity of our public healthcare be strong enough to contain it? I hope it is.

Q: Did the discovery of this groundbreaking new therapeutic approach make you more optimistic (when it comes to containing and limiting the damage of Covid-19)? In which sense (where was your optimism before the discovery)?

A: I was optimistic before, as I believe that, same as for many infectious diseases in the past, also for this disease, effective therapeutic and preventive measures will be found and used. This work further increased my optimism. Of course, this is an initial study, and this is only one of the potential means in the therapeutic, preventive and hygienic arsenal. More research and confirmation will be needed. Yet, even at this stage, the clear positive result of this study shows that it is indeed possible to improve the outcomes for COVID-19 patients even in severe conditions. Moreover, it gives more hope that effective treatments can be sought and found also for other aging-related infectious diseases and conditions.

Q: Is there an explanation regarding the reasons why Covid-19 seems to pardon children and affects the most elder individuals, especially men?

A: There is yet no clear or fully agreed explanation. But a plausible cause may be due to the so called immuno-senescence phenomenon, or the inability of the aging immune system to cope with new threats and restore the immune balance following the infection. In men the immuno-senescence effects are often more strongly present than in women. Thus, aging appears to be the main risk factor for this disease and if we really wish to defeat this epidemic, we need to address this main risk factor, in other words, we need to therapeutically intervene and ameliorate the degenerative aging process. The proposed mesenchymal stem cell therapy shows the so-called immuno-modulation effects or the ability to generally improve the immune system, help restore the immune balance after disturbances, especially for the elderly. And this can be the more general explanation for its effects against the aging-related COVID-19 pneumonia, as well as potentially other aging-related diseases.

Q: How did you manage to find so fast a treatment that is responding so well?

A: The mesenchymal stem cell treatment has been researched and developed by Dr. Zhao and his team for many years, and indicated positive effects for multiple health conditions. It is exactly because of the common and critical role of the immune system impairment in all these conditions, that the treatment developed by Dr. Zhaos team was already in place and could be immediately used also for this condition dependent on the immune function. Moreover, the success of this therapy against COVID-19 can further boost the research and therapy of other immunity-dependent health conditions and diseases, especially aging-related diseases, due to the common mechanisms of action.

Q: How may this discovery change the game?

A: Unlike other public health measures, like quarantine and hygiene, that can be very quickly applied, the research, development, regulatory approval and application of new therapies is a much slower process. So we should first of all apply the public health measures to contain the epidemic. But the hope is that this therapy will undergo further research and validation as soon as possible, and in case of validated efficacy and safety, will be used in as many patients who need it as possible, as soon as possible. That is exactly why we need to accelerate the research, development and application of promising new therapies. When the new therapy enters wide clinical practice, there are grounds to believe it can improve the health and even save the lives of many patients, not only suffering from COVID-19, but also other conditions.

Q: Which was the response/reaction of authorities after you published the results of your research?

A: The outreach to the authorities in several countries has only started. Moreover, the study is only initial and it is too early to make policy recommendations. A larger validation study is required. Yet, if there is even a slight possibility this could become a life-saving therapy for COVID-19 patients and others, this opportunity should not be missed by the decision makers.

Q: Some treatments are more expensive than others. Will the treatment you discovered be accessible to people, or the cost for producing it will limit its accessibility?

A: The cells for this treatment can be mass produced and can be rather affordable. Of course, the actual price will depend both on the scale of production and pricing policies. And this is already a question that goes beyond pure technology, but becomes a question about the social means to make new therapies available to all. This should also be a crucial part of the public discussion about the social need to promote the rapid research and development as well as broad application of new therapies that are proven to be safe and effective.

Q: Which are the best measures a country can take to limit the spread and the consequences of the novel coronavirus?

The usual quarantine and public hygiene measures are the most feasible and effective: minimization of large gatherings, minimization of travel, cleanliness. We should hope and work for new effective therapies to arrive as soon as possible. But so far public health measures are the most effective and feasible.

Ilia Stambler is an IEET Affiliate Scholar. He completed his PhD degree at the Department of Science, Technology and Society, Bar-Ilan University. His thesis subject, and his main interest, is the History of Life-extensionism in the 20th Century.

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A new therapeutic approach against COVID-19 Pneumonia - Institute for Ethics and Emerging Technologies

Toxicity minimal with novel transplantation approach for transfusion-dependent thalassemia – Healio

ORLANDO Nonmyeloablative conditioning in combination with post-transplant cyclophosphamide and thiotepa appeared feasible for patients with severe transfusion-dependent thalassemia undergoing bone marrow transplantation, according to results of a phase 1 study presented at TCT | Transplantation & Cellular Therapy Meetings.

Researchers noted the need for a phase 2 study to identify the optimal regimen to balance improved thalassemia-free survival with the least toxicity.

We hypothesized that post-transplant cyclophosphamide would overcome the engraftment barrier, reduce rejection and improve transplant and thalassemia-related outcomes for patients with different platforms, Dilan A. Patel, MD, clinical fellow in the hematology/oncology division at Vanderbilt University Medical Center, told Healio. The most favorable thing we found was minimal acute and chronic graft-versus-host disease, no cases of extensive chronic or grade 3 to grade 4 acute GVHD, and minimal transplant-related toxicities in terms of infectious complications.

Previous studies have shown that post-transplant cyclophosphamide allows for allogeneic hematopoietic stem cell transplantation across the HLA barrier. However, allogeneic HSCT can be performed only for some patients with severe transfusion-dependent thalassemia because of limited donor availability, graft rejection and regimen-related toxicities.

Allogeneic HSCT can be performed only for some patients with severe transfusion-dependent thalassemia because of limited donor availability, graft rejection and regimen-related toxicities.

Source: Adobe.

Patel and colleagues analyzed nine patients with severe transfusion-dependent thalassemia who received a common conditioning regimen of anti-thymocyte globulin dosed at 4.5 mg/kg, fludarabine at 150/m2, cyclophosphamide at 29 mg/kg, thiotepa at 10 mg/kg 7 days before transplant, and total body irradiation at 200 cGy.

Additionally, researchers administered GVHD prophylaxis consisting of cyclophosphamide at 50 mg/kg on days 3 and 4 after transplant, mycophenolate mofetil and sirolimus.

To improve engraftment rates, patients underwent preconditioning with hydroxyurea at 30 mg/kg for 60 days.

Two patients received transplants from matched related donors, whereas four received them from haploidentical donors and three received them from matched unrelated donors.

Median follow-up was 371 days.

Results showed one case of graft failure at day 32 after transplantation in the haploidentical group. The other eight patients (89%) successfully engrafted.

Researchers observed two cases each of mild gut and skin acute GVHD, and one case each of limited gut and skin chronic GVHD.

All patients remained alive at the time of reporting, with a thalassemia-free survival rate of 100% for the matched related and matched unrelated donor groups. No statistical differences existed between groups according to neutrophil or platelet engraftment, age, total nucleated cell dose or CD34-positive cell dose.

All patients remained transfusion independent, and none who underwent engraftment needed long-term immunosuppression therapy.

The only way to know if these results apply to more patients is by doing a larger phase 2 study, Patel said. In our cohort, we have pediatric and young adult patients, but we also need to know if this applies to older adults, as well. Gene therapy is being used for thalassemia right now, but on a larger scale I think transplant is the best overall option. by John DeRosier

Reference:

Patel DA, et al. Abstract 329. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.

Disclosures:

Patel reports no relevant financial disclosures. Please see the abstract for all other authors relevant financial disclosures.

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Toxicity minimal with novel transplantation approach for transfusion-dependent thalassemia - Healio

Hatteras Island Cancer Foundation Celebrates 20 Years with Upcoming Annual Gala – Island Free Press

Laney Howell

The story of the Hatteras Island Cancer Foundation started 20 years ago with a relative newcomer to the island who was amazed by the generosity and support of her new hometown community.

Laney Howell, who was born and raised in Scotland Neck, N.C., moved to Hatteras village in 1996, and was diagnosed with breast cancer shortly after her arrival. After undergoing surgery in 1997, the next 4.5 years of her life entailed an exhausting regimen of chemotherapy, radiation, and stem cell replacement therapy, and multiple long drives to reach specialized medical facilities off the island.

But Laney said at the time that she was surprised and thrilled that her new friends on Hatteras Island did everything possible to make her life more comfortable. Her Hatteras community continually pitched in to bring her meals, clean her house, care for her family, and drive her to medical appointments in Elizabeth City and Norfolk.

This sparked an idea to pay the communitys kindness forward, and reach more island cancer survivors in need, and not long after, the Hatteras Island Cancer Foundation (HICF) was born.

Island Free Press Co-Founder Irene Nolan was one of ten original locals who agreed to serve on the initial HICF board, and she wrote about the newly launched group as Editor of the now defunct Island Breeze in February of 2001. At this point just a couple months into the endeavor the all-volunteer group already had a board, officers, by-laws, and was ready to start raising money.

And the handful of folks involved in the HICFs first few months already saw the prospect of things to come.

The group has the potential to make a major contribution to the lives of Hatteras cancer patients and their families, Irene wrote in her 2001 article. And she was right.

Now, twenty years later, the organization has more than met their primary goal to raise funds and offer financial support for cancer patients to help them pay for medical bills, travel expenses for themselves and their care givers, and other costs that arent reimbursed by insurance.

To date, the Hatteras Island Cancer Foundation has assisted over 189 islanders with cancer and their families, with grants in excess of $945,000, and the enthusiasm and fundraising efforts have never slowed down in the past 20 years

Residents and visitors familiar with the island community encounter HICF-sponsored initiatives throughout the year. HICF sponsors the annual chowder cook-off at Day at the Docks in September, hosts a 5K race in October, and publishes a tempting cookbook with local recipes plucked from generations of local families.

But one of the cornerstone events that has been ingrained in the HICF since it was founded is the annual HICF Gala in April, and this years event which proudly highlights this 20-year benchmark promises to be bigger and better than ever.

The Hatteras Island Cancer Foundations very first fundraiser was the annual dance, which took place in in March, 2001, and featured live music from the Embers. The $50 tickets for the gala sold out quickly, and the event was such a success that it solidified the groups prominence on the island, and was a recurring fundraiser in the years that followed.

2020 marks the 20th anniversary of the gala, and the events popularity hasnt dwindled in the last two decades.

For this years gala, guests will be treated to live music from the band Trainwreck, heavy hor doeuvres from acclaimed local chef Dee Callahan, a raffle with a basket of gift certificates from area restaurants, and a champagne toast at 7:30 p.m. to celebrate 20 years of hard and dedicated work. Island Hopper will also be providing complimentary taxi service for attendees who want to indulge, and the gala will once again take place at the Hatteras Village Civic Center the hometown of HIFC, and the village where the organization was born.

But the event will also feature a tribute to honor founder Laney Howell, the original HICF board, and everyone who has served since the HICF was founded in November, 2000.

With hundreds of supporters over the year, the 2020 gala is particularly special, simply because it marks a time to look back and give thanks to everyone in the community who has made a contribution towards making the lives of their fellow islanders just a little bit easier.

Sadly, Laney had a recurrence of her cancer shortly after the HICF was founded, and she passed away on July 5, 2001, surrounded by her family and friends, at the age of 48.

But with the success of the first fundraising dance, Laney and her friends saw a spark of what their new group could accomplish, and that spark has certainly ignited into one of the most dedicated and recognized non-profit organizations on the island.

The legacy of Laney and the original boards dream definitively lives on. And this years gala is an opportunity to take stock, give gratitude, and look ahead to many more years of helping Hatteras Islands cancer survivors in need.

Cant make the dance but would still like to donate? Click here.

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Hatteras Island Cancer Foundation Celebrates 20 Years with Upcoming Annual Gala - Island Free Press

Scientists Grapple with US Restrictions on Fetal Tissue Research – The Scientist

At several labs across the US, researchers use fetal tissue from humans to investigate everything from viral infections to the developing brain. Such studies have been ongoing for decades, as have politically fraught debates about this research, because it primarily relies on tissue donated after terminated pregnancies.

Last summer, President Donald Trumps administration announced that it would be placing restrictions on experiments involving fetal tissue obtained from elective abortions, which included banning government scientists from using this material for research and applying increased scrutiny for National Institutes of Health (NIH) grant proposals from nongovernmental scientists.

Researchers say that the new restrictions on fetal tissue research have required them to change their plans for future work or to search for alternative sources of funding. Its impacted almost all of the facets of the lab, says Carolyn Coyne, a microbiologist at the University of Pittsburgh who uses fetal tissue to study how viruses penetrate the placenta.

Its affected pretty much every grant application that that weve written.

Mana Parast, University of California, San Deigo

One of the main concerns, according to several researchers who spoke to The Scientist,is the lack of clarity regarding what the NIH will require in grant applications for this work. The Department of Health and Human Services (HHS), which oversees the NIH, has stated that it would put together a new ethics advisory board to review such proposals. Last week (February 20), HHS posted a notice indicating its intent to convene the NIHs fetal tissue ethics advisory board in 2020. In a written statement to The Scientist,the NIH states that it is in the process of setting up the Ethics Advisory Board for the purpose of evaluating research proposing the use of human fetal tissue from elective abortion.

Scientists are waiting to find out who will be appointed to the board and how it will evaluate proposals once it convenes. [Well] see whether the administration is going to act in good faith and appoint a decent ethics review committee, or if theyre going to ignore the value of the scientific and medical research that needs to be done in this area and let ideology weigh out over logic, says Lawrence Goldstein, a stem cell scientist at the University of California, San Diego, whose lab has worked with fetal cells in the past. The fetal tissue that were talking aboutif we dont use it for research, it will be discarded. Thats the choice. Discard the fetal tissue in the in the trash, or use it for valuable research.

This is not the first time such a ban has been put in place. In 1988, former US President Ronald Reagan placed similar restrictions on federal funding for fetal tissue studies, which stayed in place until President Bill Clinton overturned them during the first year of his term in 1993.

Fetal tissue used for research is primarily obtained from elective abortions, which women can consent to donate after deciding to terminate a pregnancy. This is because there are some major limitations to tissue obtained through other means, such as miscarriages, according to Anita Bhattacharyya, a stem cell scientist at the University of Wisconsin-Madisons Waisman Center. Supply is limited and the underlying factors that lead to pregnancy loss can complicate experiments. On top of that, such events often happen unexpectedly, meaning that the collected tissue is not always intact. We would worry about using poor quality tissue as a foundation for the work we do, says Bhattacharyya, who uses donated fetal brain tissue to study brain development and disorders such as Down syndrome and fragile X syndrome.

Bhattacharyya says that although her lab currently has the tissue it needs to complete experiments from a prior grant, shes not comfortable submitting proposals for studies that require obtaining new fetal tissue. Its because I dont know whats going to happen. If I spend hours writing a grant that I think is really good science, and I send it to NIH . . . its going to get stuck there, Bhattacharyya explains. Were so busy as scientists that to just write a grant that isnt going to go anywhere is a waste of our time.

As such, her projects may suffer. According to Bhattacharyya, not only is brain development difficult to study in model organisms such as rodents, but fragile X and Down syndrome in particular are difficult, if not impossible, to model in animals. Induced pluripotent stem cells (iPSCs), which can be generated by reprogramming cells from skin or blood in adults, have offered an alternative means of studying the development and disorders of the brain, yet researchers still need to validate the results they obtain, Bhattacharyya says. Really, the only way to do that is using fetal tissue.

In addition to cells and tissue from the fetus itself, the restrictions on NIH funding were also applied to other biological materials obtained in the process of abortions, such as umbilical cord, placenta, and amniotic fluid. While some of these can be useful to scientists when collected after birth, placental tissue obtained in this way has limitations. Full term placentas are actually aged tissues, explains Coyne. If were studying a full-term placenta post-delivery, the gnawing question is: Has that placenta changed from the placenta that exists in the first or second trimester?

Mana Parast, a stem cell and placental biologist at the University of California, San Diego, who studies placental development and disorders, tells The Scientist that while the policy change has left ongoing projects unscathed, its affected pretty much every grant application that that weve written since then. While Parasts team has used fetal tissue in the past, they are now focusing on using iPSC-based models. However, like Bhattacharyya, she notes that this isnt the perfect solutionas these models are fairly new and not yet broadly accepted, it is still necessary to validate them with cells from human placentas.

Coyne says that in addition to limiting access to grants for her research, the restrictions have also made it more difficult to procure tissue. A lot of major medical schools have federally funded tissue banks, Coyne explains. Our institutional tissue bank has been affected by this such that we cant obtain tissue from elective terminations anymore.

For researchers who have been able to obtain funding from alternative sources, such as philanthropists or private foundations, the effects of the restrictions have been minimal. Thomas Reh, a biologist at the University of Washington whose team uses fetal tissue to study the developing retina, says that his groups work is currently supported by a grant from the Open Philanthropy Project, a nonprofit organization. When the political climate gets more restrictive, private donors will often step in, Reh says. I wont say that works for everybody, or that it works all the time. At least in my own case, this is whats allowed me to sort of fill these gaps when [restrictions on fetal tissue] happen.

Its the next generation of trainees that are going to be most impacted, not just because they cant get funding, but if I were one of them, I would think to myself, is this really an area that I want to specialize in?

Carolyn Coyne, University of Pittsburgh

Andrew McMahon, a stem cell scientist at the University of Southern California, still has about a year left before he needs to apply for more funding, and hes started looking into potential alternatives to NIH. My understanding is that its not entirely clear at the moment what that process is going to be, McMahon says. Ive been using the time to obtain non-NIH funding to support aspects of the research that I would have tried to get NIH funding [for] in the future.

Private funds are not available to everyone, and can be more difficult for researchers in some fields to obtain than others. For some of the disorders that I work on, the major private funding foundation does not allow fetal tissue research, Bhattacharyya says. And sometimes the foundation funding can be quite a bit less than NIH funding.

For researchers in some states, nonprofits are not the only option. In California, the states stem cell agency, the California Institute for Regenerative Medicine (CIRM) has provided funding for stem cell studies using fetal tissue since it was founded in 2004. That fund is about to run out, but a bill that would provide $5.5 billion in funding to CIRM will come before voters in November.

That will hopefully provide funding for areas of fetal tissue research that involves stem cells, Goldstein says. But . . . its ridiculous to rely on one or two states to self-fund, because we dont have all of the best and brightest [scientists], and it means lots of students and postdocs will train in areas where federal training support will be unavailable to them.

Goldstein isnt the only one concerned that the most profound effect of the governments restrictions will be on early-career investigators and trainees. While established researchers may be able to circumvent the effects of the restrictions in the short term, the ramifications for trainees in this field will likely be much longer-lasting, Coyne says. Its the next generation of trainees that are going to be most impacted, not just because they cant get funding, but if I were one of them, I would think to myself, is this really an area that I want to specialize in and get into?

One scientist, who asked to remain anonymous for fear of being harassed by anti-abortion activists, tells The Scientist that the restrictions have been a source of huge stress and anxiety for his lab, which he only established a few years ago. He adds that while his team has pivoted to using animal models and organoids generated from iPSCs, these are imperfect models of the developing human brain, which is the focus of his work.

It makes no sense to limit this research, given that the tissue from abortions will get discarded now that donation is not an option, Parast says. Were not talking about encouraging this procedurewere trying to use the material from patients who have already decided to undergo this procedure in order to be able to help other women.

Diana Kwon is a Berlin-based freelance journalist. Follow her on Twitter@DianaMKwon.

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Scientists Grapple with US Restrictions on Fetal Tissue Research - The Scientist

CAR T Cells to Go? Outpatient Therapy Can Be Safe – Medscape

ORLANDO, Florida Chimeric antigen receptor (CAR) T-cell therapy can be safely delivered in the outpatient setting, which could make the life-extending treatment available to patients who don't have access to a major teaching hospital or treatment center, contend investigators who analyzed data from three clinical trials.

Looking at outcomes for patients with large B-cell lymphomas (LBCL) who were treated with the CAR T-cell construct lisocabtagene maraleucel (liso-cel) in the outpatient setting at both university-based and nonacademic medical centers in three clinical trials, Carlos Bachier, MD, from the Sarah Cannon Blood Cancer Network in Nashville, Tennessee, and colleagues found that the incidences of severe adverse events were relatively low and manageable.

"Outpatient administration of liso-cel and subsequent monitoring were successfully implemented in multiple clinical trials at both university and nonuniversity sites," he said here at the Transplantation and Cellular Therapy annual meeting.

Dr Carlos Bachier

The need to monitor and treat serious side effects from CAR T therapy, such as the cytokine release syndrome (CRS) and neurologic toxicities, has previously limited the therapy to major treatment centers with extensive resources. Yet most patients in the US with relapsed or refractory large B-cell non-Hodgkin lymphoma are treated at nonacademic centers where cancer therapies are typically delivered in outpatient infusion centers, Bachier said.

"Infusion and monitoring of patients receiving CAR T-cell therapy in the outpatient setting can lead to wider utilization and improved access," he said.

To get a better idea of the safety and efficacy of CAR T-cell therapy in the outpatient setting, Bachier and colleagues examined outcomes from the phase 1 TRANSCEND NHL 001 trial of liso-cel in one or two doses for a variety of aggressive lymphoma histologies, conducted in both university-based and nonuniversity centers; the phase 2 TRANSCEND-OUTREACH trial of outpatient liso-cel therapy after two or more prior lines of therapy against various lymphomas and lymphoproliferative disorders, conducted in nonuniversity centers; and the phase 2 TRANSCEND-PILOT-017006, testing liso-cel in patients with LBCL relapsed or refractory after a single line of immunochemotherapy who were ineligible for either high-dose chemotherapy or stem cell transplant. This trial was conducted in both university and nonuniversity settings.

In OUTREACH and PILOT, liso-cel was administered at a dose of 100 x 106 CAR-positive T cells; in TRANSCEND, it was given at doses of 50, 100, or150 x 106.

To qualify for outpatient administration and monitoring, both university centers and nonuniversity specialty oncology centers had to have at least hematopoietic stem cell therapy (HSCT) or phase 1 trial capability, an outpatient infusion center or inpatient infusion unit with same-day discharge; an affiliated aphereseis center; and a multidisciplinary medical team that can coordinate care between inpatient and outpatient settings, have standard operating procedures for outpatient monitoring and admissions when necessary, and an oncologist on call at all times.

In addition, each center had to have one designated hospital for care of CAR T-cell recipients with staff trained to manage typical CAR T-cell toxicities and a ready supply of tocilizumab (Actemra, Genentech) for treating CRS.

For their part, patients needed to have caregiver support and stay within 1 hour travel of the treatment center for the first 30 days after infusions, had to commit to returning to the site for immediate medical evaluation as necessary, and had to be educated about the early signs and symptoms of CRS and neurologic toxicities.

The analysis included data on 44 patients with a median age of 62 years (range 24 to 82), including 25 enrolled in TRANSCEND, 13 in OUTREACH, and 6 in PILOT. Eighteen patients were age 65 or older, 12 had high tumor burden, and 6 had lactate dehydrogenase (LDH) levels of 500 U/L or higher.

Treatment-related adverse events (TEAEs) occurring in at least 25% of outpatients were similar to those among all patients in TRANSCEND, with the most frequent grade 3 or 4 events being neutropenia, anemia, and thrombocytopenia. There were no treatment-related deaths among those monitored as outpatients.

CRS of any grade occurred in 12 of 25 outpatients (48%) in TRANSCEND, in 5 of 13 (38%) in OUTREACH, and in none of the 6 outpatients in PILOT. Grade 3 or 4 CRS was seen in 1 outpatient in TRANSCEND, but in none of the other patients in the other two trials.

Grade 3 or 4 neurologic events occurred in two outpatients in TRANSCEND, but were not seen in any outpatients in OUTREACH or PILOT.

Three patients in TRANSCEND and two in OUTREACH received either tocilizumab or corticosteroids for CRS, and five patients in TRANSCEND received corticosteroids for neurologic adverse events. Prolonged grade 3 or greater cytopenias were seen in three patients in TRANSCEND, five in OUTREACH, and one in PILOT.

The median onset of CRS was 5 days, and the median onset of neurologic toxicities was 8 days among all outpatients, and was similar to combined inpatient and outpatient population in TRANSCEND. The median duration of the events 6 days for CRS, 16 days for neurologic events was also similar to that seen in TRANSCEND.

Of the 44 patients from all three trials, 24 (55%) were hospitalized after liso-cel administration, for a median of 6.5 days (range 2-23). The median time to hospitalization was 5 days. One third of the hospitalizations were for either CRS or neurologic events. There were 2 cases of ICU admissions after liso-cel administration, for a median ICU stay of 4 days.

In all, 45% of outpatients did not require hospitalization, and there was no increase in ICU admissions compared with inpatients, Bachier pointed out.

The overall response rate was 80%, with a complete response rate of 55%, similar to that seen in TRANSCEND, he said.

In an interview with Medscape Medical News seeking objective commentary on the findings, Yago Nieto, MD, from the University of Texas MD Anderson Cancer Center in Houston, said that he would be comfortable with CAR T-cell therapy in the outpatient setting, provided that several key components of care are in place.

"It requires an organized effort to be able to see those patients in an outpatient clinic weekdays and weekends, having every contingency discussed beforehand, including for ICU team members to admit patients into the ICU if necessary which is unusual, particularly with liso-cel but it has to be all worked out in advance in a multidisciplinary effort," he said.

Nieto comoderated the session where the data were presented, but was not involved in the study.

Comoderator Mazyar Shadman, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, who was not involved in the study, told Medscape that his center treats patients with CAR T therapy in the outpatient setting.

"But it's important to know that when you talk about outpatient care, it's not your outpatient clinic where you see patients once a week," he said. "These are intensive outpatient centers. We have a team that's just outpatient, but we see these patients on a daily basis, we have dedicated nurses and practitioners, and we have labs and immunotherapy services for getting results quickly."

"I feel comfortable giving CAR T therapy to a patient in this setting," he added, "but not to a patient being treated in the middle of nowhere."

The study was funded by Juno Therapeutics, a Bristol-Myers Squibb company. Bachier disclosed advisory board activities for various companies, not including Juno or BMS. Nieto disclosed research funding and consultancy for various companies not including the sponsors of this study. Shadman disclosed research funding, honoraria, and consultancy with various companies not including Juno or BMS.

Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR 2020: Abstract29. Presented February 19, 2020.

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CAR T Cells to Go? Outpatient Therapy Can Be Safe - Medscape

TO YOUR HEALTH: Inflammation can drive triple-negative breast cancer – Dover Post

Study at ChristianaCare Cawley Center for Translational Cancer Research

While radiation is successfully used to treat breast cancer by killing cancer cells, inflammation caused as a side-effect of radiation can have a contrary effect by promoting the survival of triple-negative breast cancer cells, according to research published online in the International Journal of Radiation Biology by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCares Helen F. Graham Cancer Center & Research Institute.

Accounting for 15-20% of all breast cancers, triple-negative breast cancer is faster growing than other types.

Sims-Mourtadas latest study, Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells, brings scientists closer to understanding the mechanisms behind this aggressive and hard-to-treat cancer. It shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem breast cancer cells.

This is the good and the bad of radiation, Sims-Mourtada said. We know radiation induced inflammation can help the immune system to kill tumor cells thats good but also it can protect cancer stem cells in some cases, and thats bad.

She added, Whats exciting about these findings is were learning more and more that the environment the tumor is in its microenvironment is very important. Historically, research has focused on the genetic defects in the tumor cells. Were now also looking at the larger microenvironment and its contribution to cancer.

The term triple-negative breast cancer refers to the fact that the cancer cells dont have estrogen or progesterone receptors and also dont make too much of the protein called HER2. The cells test negative on all 3 tests. These cancers tend to be more common in women under age 40, who are African-American, Latina or who have a BRCA1 mutation.

My work focuses on cancer stem cells and their origination, Sims-Mourtada said. They exist in many cancers, but theyre particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth.

She and her team applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. As yet unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.

For women living in Delaware, Sims-Mourtadas research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

At ChristianaCare, we are advancing cancer research to help people in our community today, while we also advance the fight against cancer nationwide, said Dr. Nicholas J. Petrelli, Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute. Dr. Sims-Mourtadas research is a dramatic step toward better treatments for triple-negative breast cancer.

To advance her research on inflammation, last year Sims-Mourtada received a $659,538 grant from the Lisa Dean Moseley Foundation. The three-year grant will enable her and her team at the Cawley Center for Translational Cancer Research to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and a possible therapy for this particularly difficult cancer.

Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing, Sims-Mourtada said.

Sims-Mourtadas research team previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.

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Arctic Medical Center: Regenerative Medicine & Stem Cell …

About Arctic Medical Center

Arctic Medical Center offers advanced services to adult patients from in and around Anchorage, Alaska. As a premier medical center, the team of physicians, nurse practitioners, and other health care providers, which includes a chiropractor, provides customized health care. They combine advanced medical treatments, state-of-the-art regenerative medicine, chiropractic care, and other integrative medicine therapies like massage therapy to help patients lead healthy, pain-free, active lives.

Arctic Medical Center treats a wide range of ailments, including neck, back, hip, and joint pain, as well as sexual health. Their goal is to offer highly personalized care not only to relieve painful symptoms but also to heal the underlying condition causing them.

Research shows that regenerative medicine techniques, such as platelet-rich plasma (PRP) injections and mesenchymal stem cells, may stimulate and support the natural healing response of the human body. Arctic Medical Center explores every treatment option available with patients to find the most-effective solution.

The team of expertly trained physicians and wellness providers are committed to serving their patients and the community. New patients are welcome at Arctic Medical Center, and appointments are available by calling the practice or booking online.

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New study identifies trigger that turns dormant cancer stem cells into active ones – Benzinga

A new study released today in STEM CELLS identifies, for the first time, two morphologically and functionally different types of cancer stem cells found in cervical cancer.

DURHAM, N.C. (PRWEB) February 26, 2020

A new study released today in STEM CELLS identifies, for the first time, two morphologically and functionally different types of cancer stem cells found in cervical cancer. Of the two types, one exhibits an overexpression of cPLA2, a key enzyme that triggers the transformation of dormant cancer stem cells into active ones, resulting in cervical cancer metastasis and recurrence. The information in this study could lead to new targets for treatments to halt tumor recurrence and metastatic spread. Also, it might accelerate the development of combination therapies.

The current standard of treatments for cervical cancer the second leading cause of cancer death in young women worldwide is radiotherapy and chemotherapy. However, the cancer's resistance to chemotherapy and radiation, combined with a tendency to metastasis in the lymph nodes or recur in the pelvis, leaves doctors searching for more effective treatments.

Cervical cancer stem cells (CCSCs) are considered the major culprit behind the cancer's ability to overcome these treatments. At the same time, a majority of cancer stem-like cells or tumor-initiating cells remain dormant. It takes a change in their microenvironment to spur them to metastasize.

"The mechanisms responsible for this must be identified to design more suitable therapies for the different subpopulations of cancer stem cells (CSCs) in various tissue-specific cancers," said Hua Guo, Ph.D., who headed up the investigation along with Yuchao He, Ph.D. The two are colleagues at Tianjin Medical University Cancer Institute and Hospital. Researchers at Tianjin University of Traditional Chinese Medicine and at the Center for Translational Cancer Research, Peking University First Hospital, also participated in the study.

Although several cell surface antigens have been identified in CCSCs, these markers vary among tumors because of CSC heterogeneity. However, whether these markers specifically distinguish CCSCs with different functions is unclear. The study published in STEM CELLS sought to resolve this question. And in fact, its findings demonstrate that CCSCs exist in two biologically distinct phenotypes, characterized by different levels of cPLA2 expression.

"Our study showed for the first time that overexpression of cPLA2 results in a phenotype associated with mesenchymal traits, including increased invasive and migration abilities. On the other hand, CCSCs with cPLA2 downregulation show dormant epithelial characteristics," said Dr. Guo. "In addition, cPLA2 regulates the reversible transition between mesenchymal and epithelial CCSC states through PKC, an atypical protein that governs cancer cell state changes."

Dr. He added, "Now that we know cPLA2 triggers this transformation, we believe that cPLA2 might be an attractive therapeutic target for eradicating different states of CCSCs to eliminate tumors more effectively."

"The novel study by Dr. Guo and team is of very high importance in understanding the transition between dormant cancer stem cells, which evade chemotherapy and radiation treatments, and actively dividing cells which can be better targeted, said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. "I applaud the group for this important discovery which will help researchers develop better treatments for cervical cancer."

###

The full article, "cPLA2 reversibly regulate different subsets of cancer stem cells transformation in cervical cancer," can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3157.

Figure Caption: This study revealed that there are two morphologically and functionally distinct cancer stem cell populations regulated by cPLA2 in cervical cancer. cPLA2 might be a unique marker to identify different cancer stem cell populations and trigger quiescent epithelial cancer stem cells transform to invasive mesenchymal states. Overexpression of cPLA2 resulted in a CD44+CD24- phenotype with mesenchymal traits, whereas cervical cancer stem cells (CCSCs) with cPLA2 downregulation expressed CD133 and showed epithelial characteristics. cPLA2, as a key role to reversely regulate CCSCs states and EMT, might provide innovative therapeutic strategies intended to halt tumor recurrence and metastasis.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

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UCLA raises $5.49 billion in one of most ambitious campaigns ever by a public university – UCLA Newsroom

The Centennial Campaign for UCLA, one of the most ambitious fundraising campaigns ever by a public university, has raised $5.49 billion. As UCLA enters its second century, the funds are already supporting a broad array of priorities, including student scholarships and fellowships, faculty research, and programs that enrich communities in Los Angeles and beyond.

The campaign launched publicly in May 2014 and closed in December 2019, in the midst of UCLAs 100th year. During the initiative, nearly 220,000 donors from all 50 U.S. states and 98 additional countries gave more than 574,000 gifts to advance causes across campus and in communities in Southern California and around the world.

Approximately 95% of those gifts were less than $10,000, and 81% were less than $1,000, indicating the broad-based support for UCLAs mission.

UCLA also received transformative philanthropic commitments of more than $100 million, including Marion Andersons giving for students, faculty and facilities at the UCLA Anderson School of Management; David Geffens gifts for medical student scholarships and the Geffen Academy at UCLA; Meyer and Renee Luskins giving to name the school of public affairs and build a campus conference center; and Henry and Susan Samuelis gifts to expand engineering education and research.

As we celebrate UCLAs first hundred years, the Centennial Campaign for UCLA has exceeded its goals and engaged students, faculty, friends and leaders in setting up the university for an even more remarkable second century, UCLA Chancellor Gene Block said. We are so grateful to each and every person who has participated in this extraordinary effort.

Campaign gifts cross campus, causes and communities

Funds raised through the campaign already are making a difference across the campus, including supporting students in a diverse range of fields. Such support includes humanities fellowships established by Jordan and Christine Kaplan and Ken Panzer; scholarships created by the cast and crew of hit television show The Big Bang Theory for students in science, technology, engineering and math fields; scholarships for dentistry students created by Bob and Marion Wilson; and scholarships for public health students established by Jonathan and Karin Fielding.

Steve Tisch and Shirley and Walter Wang both established scholarships for students from middle-income families; faculty member Ellen Carol DuBois donated to support transfer students; and the family of the late Bill Steinmetz, a UCLA alumnus and World War II veteran, gave to support student veterans.

Campaign giving for scholarships leveraged funds through matching challenges, such as those initiated by Miguel Garca-Garibay, dean of the UCLA College division of physical sciences, and Block, who designated student support as a campaign and continuing priority. Every new scholarship will help make a high-quality education affordable for high-achieving students of all backgrounds. UCLA already ranks No. 1 among the nations top-tier universities for enrolling low- to middle-income students, and more of its graduates move up two or more income levels, according to The Equality of Opportunity Project. During the Centennial Campaign, UCLA raised $665 million for student support.

Many other campaign gifts created endowed chairs to recruit and retain stellar faculty: Iris Cantor established the universitys 500th chair with a gift to the Iris CantorUCLA Womens Health Center, and the Ralph and Shirley Shapiro family established several faculty chairs during the campaign in dentistry, disability studies, law, nursing, pediatrics and other areas bringing the total number of chairs they have established at UCLA to more than 20.

Other donors enhanced the campus with lead gifts for state-of-the-art facilities. With the Eugene & Maxine Rosenfeld Hall for medical education, the Evelyn and Mo Ostin Music Center, the Mo Ostin Basketball Center and the Wasserman Football Center, construction has transformed UCLA during the course of the campaign. In Westwood and beyond, the arts have benefited from Marcy Carseys and Stewart and Lynda Resnicks gifts to renovate the Hammer Museum at UCLA and Margo Leavins gift to refurbish graduate art studios in Culver City.

Throughout the campaign, philanthropists supported UCLA initiatives in a wide array of fields with real-world relevance:

Alumni and friends invest in UCLA

The Centennial Campaign, which was co-chaired by Tony Pritzker and UCLA alumnus Garen Staglin, counted the contributions of nearly 220,000 donors, including nearly 127,000 first-time donors and more than 108,000 alumni donors.

I truly believe in UCLA as a unique public research institution that benefits students from every walk of life, the city of Los Angeles and the world at large, said Pritzker, who is not a UCLA alumnus but serves as a tireless benefactor and champion of the campus. Ensuring a successful start to its second century is an investment not only in the university and its students but in everyones future.

Staglin and his wife, Shari, launched the organization One Mind, which bridges gaps in mental health research and patient support, and they have been strong advocates for the UCLA Depression Grand Challenge. UCLA is leading the way in so many areas, and it has been a privilege to see alumni and friends come together to support causes close to their hearts while advancing education, research and service that change lives, he said.

UCLA makes its mark in higher education fundraising

At the time of its launch, the Centennial Campaigns $4.2 billion goal was the most ambitious fundraising goal ever announced by a U.S. public university, and UCLA surpassed that target 18 months ahead of schedule. Since then, the higher education sector has continued to see an upturn in fundraising and campaigns. According to the Voluntary Support of Education survey, giving to colleges and universities grew 6.1% in 201819.

The same survey ranked UCLA the No. 1 public university in philanthropic funds raised for 201718, and the campus was included in the Chronicle of Philanthropys special report on multiyear campaigns in April 2019. The feature highlighted the proliferation of such fundraising drives across the country, including at several other high-profile institutions across Los Angeles.

In a philanthropic landscape overflowing with opportunities to give, the success of the Centennial Campaign for UCLA speaks to donors generosity and their belief in UCLAs mission, said Rhea Turteltaub, UCLAs vice chancellor for external affairs. We take the responsibility to steward their trust very seriously, and we will continue working to ensure students access to education, secure resources for research and deliver on our commitment to public service every day.

To view campaign results, read stories about gifts and beneficiaries or learn more about giving to UCLA, visit the Centennial Campaign for UCLA site and UCLA Newsroom.

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Abu Dhabi, UAE | Stem Cell Center

Since 2000, Aesthetic Polyclinic has had the privilege to serve the residents of Abu Dhabi and Al Ain with superior Aesthetic services from Plastic surgery to Dermatology, IPL Hair removal, Cosmetic and general dentistry, slimming and body treatments and specialized skin care.

As one of Abu Dhabis top healthcare clinics, we are committed to our vision of meeting the growing needs of our clients and patients through through the continuous use of latest medical technology and services, delivered by professional, efficient and customer centric staff. We understand the true meaning of Customer service excellence and strive to achieve it through Quality, Innovation, Excellence, Customer Focus and Leading Technology.

Our organization has been focused on growing and enhancing our services. Aesthetic Polyclinic, formally known as Aesthetic Skin Care centre, started as one of the first medical spas in Abu Dhabi in 2000. In 2009 Aesthetic became a polyclinic offering Dermatology and Plastic Surgery. In 2013, we expanded our medical services into a brand new state of the art dedicated medical building which included the addition of dental and orthodontic services.

Our clinic nestles away from the pressure of everyday life, so our clients may benefit from their time with Aesthetic physically and emotionally. We at Aesthetic recognize and affirm the uniqueness of each man and woman and our image consultants strive to achieve their clients goals through advanced technology and highly skilled medical staff, who believe in creating natural looking results that are described as You just better!. Aesthetic respects each clients will of looking as good on the outside as they feel on the inside by offering individually tailored packages of care enabling them to make informed decisions to achieve their Perfect Image.

It is with great pride that I share our history and efforts within our community and thank all of our clients and patients for their continued confidence and loyalty to our organization.

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Abu Dhabi, UAE | Stem Cell Center