The potential use of CRISPR to treat disease is gaining momentum – BioNews

13 January 2020

Promising results from clinical trials give hope for using CRISPR/Cas9 genome editing to treat various heritable diseases and cancer in humans.

It has been seven years since the discovery that the CRISPR/Cas9 defence system, used by microbes to destroy viruses, could be re-engineered to edit the human genome. Since then researchers have carried out an array of experiments to explore potential applications.

Biophysist Dr He Jiankui sparked global controversy concerning the ethics of genome editing when he used CRISPR to genetically modify embryos, resulting in the birth of the first genome-edited babies (see BioNews 977).

Yet researchers worldwide have at the same time been investigating the use of CRISPR for non-heritable changes, modifying the genes in non-embryonic cells to treat a wide range of diseases.

'There's been a lot of appropriate caution in applying this to treating people, but I think we're starting to see some of the results of that work,' said Dr Edward Stadtmauer, a haematologist at the University of Pennsylvania, Philadelphia.

Over a dozen new clinical trials testing CRISPRtherapy on diseases such as cancer, HIV and sickle cell anaemia were listed on the clinicaltrials.gov database last year. One trial in its early stages used CRISPR to treat sickle cell anaemia and beta-thalassaemia, both genetic blood disorders that result in the production of an abnormal form of the oxygen-carrying protein, haemoglobin.

Two patients with these disorders were treated by CRISPR Therapeutics in Cambridge, Massachusetts, and Vertex Pharmaceuticals in Boston, Massachusetts, using CRISPR to inactivate a gene that switches off the production of an alternative form of haemoglobin. Preliminary results of the study suggest that this therapy improved some of the symptoms but the participants will need to be followed for a longer period to be sure.

Results from two other trials, one in which genome-edited blood cells were transplanted into a man to treat HIV infection, and the other in which they were transplanted into three people to treat some forms of cancer, were less successful. In both cases, the transplanted cells flourished in the bone marrow of recipients, without any serious safety concerns, but did not produce a clear medical benefit. The study has been placed on hold while researchers explore ways to boost that percentage, says Hongkui Deng, a stem-cell researcher at Peking University, Beijing, China and a lead author of the work.

Other researchers are trying to move beyond editing cells in vitro. In July 2019 a clinical trial was launched to treat Leber congenital amaurosis 10 (LCA10), a rare genetic disease that causes blindness. The trial, launched by two pharmaceutical companies, Editas Medicine in Cambridge, Massachusetts, and Allergan in Dublin, Ireland, will be the first trial that uses CRISPR to edit cells inside of the body. The researchers are testing AGN-151587 (EDIT-101), which is a novel CRISPR treatment delivered via adeno-associated virus (AAV) directly to the eye's light-sensing photoreceptor cells to remove the mutation that causes LCA10.

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The potential use of CRISPR to treat disease is gaining momentum - BioNews

What is Mantle Cell Lymphoma and How Is It Treated? – Dana-Farber Cancer Institute

Last Updated on January 10, 2020

Medically reviewed by Ann S. LaCasce, MD, MMSc

Mantle cell lymphoma is a rare, often aggressive form of non-Hodgkin lymphoma (NHL), a cancer that involves white blood cells known as lymphocytes, which help protect the body from disease. It is named for its origins in the mantle zone a ring of cells within the lymph nodes where B cells (a type of lymphocyte) grow and take on specialized functions. It comprises about 6% of all cases of NHL, usually arises during an individuals early 60s, and is more common in men than women.

The most common symptoms of mantle cell lymphoma include:

At the time of diagnosis,nearly all patients have disease that has spread beyond its initial site.

For most patients, the cause of the disease is unknown, but rates are higher among farmers and people from rural areas.

Itoccurs when B lymphocytes acquire genetic mutations that alter their functionand growth. One such abnormality, found in 90% of cases, causes B lymphocytesto overproduce cyclin D1, a protein that spurs the cells growth. Othermutations can interfere with B cells ability to produce infection-fightingantibodies, leaving patients vulnerable to certain diseases.

A definitive diagnosis requires a biopsy of an affected lymph node or other involved tissue.

Doctors use a variety of scans to determine the diseases stage, or how far it has advanced. These include:

Treatment for mantle cell lymphoma varies depending on patients age and overall health and the stage of the disease. Patients who have yet to develop symptoms and who have a relatively small amount of slow-growing disease may be recommended for active surveillance close monitoring of their health through regular checkups and lab tests. When lymphoma-related symptoms appear or tests show a worsening of the disease, active treatment may begin.

The initial treatment for aggressive mantle cell lymphoma in younger patients often includes a combination of chemotherapy drugs in conjunction with an antibody-based treatment, often followed by a stem cell transplant using patients own stem cells. Older, less-fit patients may undergo less intensive chemotherapy sometimes followed by a prolonged course of antibody therapy.

Other treatments may include drugs known as BTK inhibitors such as acalbrutinib and ibrutinib, which interfere with lymphoma cells internal growth signals.

In patients who relapse after treatment or dont respond to initial treatment, a variety of options may be available, including:

Clinical trials are currently underway of CAR T-cell therapy for patients with mantle cell lymphoma. The therapy, which uses genetically modified immune system T cells to attack tumor cells, has been shown to be effective in patients with other forms of non-Hodgkin lymphoma. Other trials are testing drugs known as bispecific antibodies, artificial proteins that can bind simultaneously to two surface proteins on cells, and targeted agents directed against specific cancer-related proteins.

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What is Mantle Cell Lymphoma and How Is It Treated? - Dana-Farber Cancer Institute

At 16, shes a pioneer in the fight to cure sickle cell disease at Boston Childrens – Boston.com

BOSTON Helen Obando, a shy slip of a girl, lay curled in a hospital bed in June waiting for a bag of stem cells from her bone marrow, modified by gene therapy, to start dripping into her chest.

The hope was that the treatment would cure her of sickle cell disease, an inherited blood disorder that can cause excruciating pain, organ damage and early death.

Helen, who at 16 was the youngest person ever to undergo the therapy, was sound asleep for the big moment.

It was a critical moment in medical science.

For more than a half-century, scientists have known the cause of sickle cell disease: A single mutation in a gene turns red blood cells into rigid crescent or sickle shapes instead of soft discs. These misshapen cells get stuck in veins and arteries, blocking the flow of blood that carries life-giving oxygen to the body and causing the diseases horrifying hallmark: episodes of agony that begin in babyhood.

Millions of people globally, a vast majority of them Africans, suffer from sickle cell disease. Researchers have worked for decades on improving treatment and finding a cure, but experts said the effort has been hindered by chronic underfunding, in part because most of the estimated 100,000 people in the United States who have the disease are African American, often poor or of modest means.

The disease also affects people with southern European, Middle Eastern or Asian backgrounds, or those who are Hispanic, like Helen.

This is the story of two quests for a sickle cell cure one by the Obando family and one by a determined scientist at Boston Childrens Hospital, Dr. Stuart Orkin, 73, who has labored against the disease since he was a medical resident in the 1970s.

Like many others affected by sickle cell, the Obando family faced a double whammy: not one but two children with the disease, Helen and her older sister, Haylee Obando. They lived with one hope for a cure, a dangerous and sometimes fatal bone marrow transplant usually reserved for those with a healthy sibling as a match. But then they heard about a potential breakthrough: a complex procedure to flip a genetic switch so the body produces healthy blood.

Scientists have been experimenting with gene therapy for two decades, with mixed success. And it will be years before they know if this new procedure is effective in the long term. But if it is, sickle cell disease could be the first common genetic disorder to be cured by manipulating human DNA.

Four weeks after the infusion of stem cells, Helen was strong enough to be discharged. At home, in Lawrence, Massachusetts, on a sofa with her mother by her side, she put a hand over her eyes and started to sob. She and her family wondered: Would it work? Was her suffering really over?

A Familys Nightmare

Sheila Cintron, 35, and Byron Obando, 40, met when she was in the eighth grade and he was a high school senior. They fell in love. Haylee, their first child, was born in 2001, when Cintron was 17.

When a newborn screening test showed that Haylee had the disease, her father asked, Whats sickle cell?

They soon found out.

As the family gathered for her first birthday party, Haylee started screaming inconsolably. They rushed her to the hospital. It was the first of many pain crises.

Doctors warned the parents that if they had another baby, the odds were 1 in 4 that the child would have sickle cell, too. But they decided to take the chance.

Less than two years later, Helen was born. As bad as Haylees disease was, Helens was much worse. When she was 9 months old, a severe blockage of blood flow in her pelvis destroyed bone. At age 2, her spleen, which helps fight bacterial infections, became dangerously enlarged because of blocked blood flow. Doctors surgically removed the organ.

After Helen was born, her parents decided not to have any more children. But four years later, Cintron discovered she was pregnant again.

But they were lucky. Their third child, Ryan Obando, did not inherit the sickle cell mutation.

As Ryan grew up, Helens health worsened. When he was 9, Helens doctors suggested a drastic solution: If Ryan was a match for her, he might be able to cure her by giving her some of his bone marrow, though there would also be major risks for her, including death from severe infections or serious damage to organs if his immune system attacked her body.

As it turned out, Ryan matched not Helen but Haylee.

The transplant succeeded, but her parents asked themselves how they could stand by while one daughter was cured and the sicker one continued to suffer.

There was only one way to get a sibling donor for Helen: have another baby. In 2017, the couple embarked on another grueling medical journey.

Obando had a vasectomy, so doctors had to surgically extract his sperm from his testicles. Cintron had 75 eggs removed from her ovaries and fertilized with her husbands sperm. The result was more than 30 embryos.

Not a single embryo was both free of the sickle cell gene and a match for Helen.

So the family decided to move to Mesa, Arizona, from Lawrence, where the cold, which set off pain crises, kept Helen indoors all winter. The family had already sold their house when they heard that doctors at Boston Childrens were working on sickle cell gene therapy.

Cintron approached Dr. Erica Esrick, a principal investigator for the trial. But the trial wasnt yet open to children.

Figuring Out the Science

Nothing had prepared Orkin for the suffering he witnessed in his 30s as a medical resident in the pediatric hematology ward at Boston Childrens. It was the 1970s, and the beds were filled with children who had sickle cell crying in pain.

Orkin knew there was a solution to the puzzle of sickle cell, at least in theory: Fetuses make hemoglobin the oxygen-carrying molecules in blood cells with a different gene. Blood cells filled with fetal hemoglobin do not sickle. But the fetal gene is turned off after a baby is born, and an adult hemoglobin gene takes over. If the adult gene is mutated, red cells sickle.

Researchers had to figure out how to switch hemoglobin production to the fetal form. No one knew how to do that.

Orkin needed ideas. Supported by the National Institutes of Health and Howard Hughes Medical Institute, he kept looking.

The breakthrough came in 2008. The cost of gene sequencing was plummeting, and scientists were finding millions of genetic signposts on human DNA, allowing them to home in on small genetic differences among individuals. Researchers started doing large-scale DNA scans of populations, looking for tiny but significant changes in genes. They asked: Was there a molecular switch that flipped cells from making fetal to adult hemoglobin? And if there was, could the switch be flipped back?

They found a promising lead: an unprepossessing gene called BCL11A.

In a lab experiment, researchers blocked this gene and discovered that the blood cells in petri dishes started making fetal instead of adult hemoglobin.

Next they tried blocking the gene in mice genetically engineered to have human hemoglobin and sickle cell disease. Again, it worked.

Patients came next, in the gene therapy trial at Boston Childrens that began in 2018.

The trial run by Dr. David Williams, an expert in the biology of blood-forming stem cells at Boston Childrens, and Esrick has a straightforward goal: Were going to reeducate the blood cells and make them think they are still in the fetus, Williams said.

Doctors gave adult patients a drug that loosened stem cells immature cells that can turn into red blood cells from the bone marrow, their normal home, so they floated free in the bloodstream. Then they extracted those stem cells from whole blood drawn from the patient.

The researchers used a disabled genetically engineered AIDS virus to carry information into the stem cells, flipping on the fetal hemoglobin gene and turning off the adult gene. Then they infused the treated stem cells into patients veins. From there, the treated cells migrated into the patients bone marrow, where they began making healthy blood cells.

With the success in adults, the Food and Drug Administration said Boston Childrens could move on to teenagers.

When her mother told her about the gene therapy trial, Helen was frightened. But the more she thought about it, the more she was ready to take the risk.

In the months after the gene therapy infusion at Boston Childrens, her symptoms disappeared.

Helen was scheduled for her six-month checkup Dec. 16. Helens total hemoglobin level was so high it was nearly normal a level she had never before achieved, even with blood transfusions. She had no signs of sickle cell disease.

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At 16, shes a pioneer in the fight to cure sickle cell disease at Boston Childrens - Boston.com

At 16, Shes a Pioneer in the Fight to Cure Sickle Cell Disease – The New York Times

In the months after the gene therapy infusion at Boston Childrens, her symptoms disappeared. But doctors had given her blood transfusions while she regrew her own red blood cells, so it was not clear if the absence of symptoms was because of the gene therapy or the transfusions.

As she recovered, Helen returned to her passion: dancing. One day, she came back from her school dance group and told her mother, My legs hurt. It feels funny. Ms. Cintron smiled. Thats soreness, she explained. Helen laughed. She had only known pain from sickle cell.

Helen was scheduled for her six-month checkup on Dec. 16. By then, all the transfused cells were gone, leaving only blood made by stem cells in her own marrow. The doctors would finally tell her whether the therapy was working.

The day before, she and her parents visited the New England Aquarium in Boston. She was able to stay outside on a cold, blustery day, watching one seal bully the others, barking and fighting. When Helen mentioned that her hands were cold, Ms. Cintrons stomach clenched in fear. But it was just a normal thing to feel on a winter day.

The next morning, Dr. Esrick delivered the news. Helens total hemoglobin level was so high it was nearly normal a level she had never before achieved even with blood transfusions. She had no signs of sickle cell disease.

Now you are like me, her father told her. I jump in the pool, I run. Now you can do it, too!

Her family, accustomed to constant vigilance, is only now getting used to normal life.

On Dec. 23, Helen and her mother flew to the familys new home in Arizona.

Helen recently described her transformed outlook on Facebook.

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At 16, Shes a Pioneer in the Fight to Cure Sickle Cell Disease - The New York Times

Doug Richards remembered – faribaultcountyregister.com | News, Sports, Information on the Blue Earth region – Faribault County Register

Faribault County recently suffered the loss of the recently retired Honorable Judge Douglas Richards.

Since 2012, Richards battled a rare form of blood cancer known as multiple myeloma. There is no cure for the cancer and since his cancer prognosis eight years ago, Richards fought tooth and nail through chemotherapy treatments and stem cell transplants which can greatly compromise the immune system.

Judge Richards became the Faribault County District Court judge back in 1995, and prior to that, was an attorney in Faribault County for many years. He earned his undergraduate degree at Hamline University and earned his degree in law at the William Michell College of Law.

Orv Terhark, Faribault County District Court stenographer for many years, now retired, worked alongside Richards.

"Judge Richards has always had remarkable patience," Terhark reflected of his friend. "It was important to him that all litigants in his courtroom had equal and ample time to be heard, no matter how hectic our schedule was."

Retired attorney Chuck Frundt recalls the State of Minnesota was considering lessening the number of judges across the state, and that included Faribault County's district judge.

"We attorneys were worried about what would happen,"?says Frundt. "Many of us Faribault County attorneys stood together and supported Judge?Richard's judgeship. We wrote letters, we called Governor Arne Carlson to let them know we needed Judge Richards."

And the state listened. Faribault County did not lose its district judge when the state lessened its judgeships.

"He was a good judge, a fair judge," says Frundt. "And when he was an attorney, as a competing attorney, he was good, he was congenial. A solid person to have in the courtroom."

Chuck's wife Rita Frundt recalls Judge Richards saying at his retirement party that he liked being an attorney, but loved being a judge.

Current Faribault County District Judge Troy Timmerman said he spent his entire career under Judge Richards when he moved to the county in 1994.

"He had a quiet strength about him," says Judge Timmerman. "He was able to maintain control of the courtroom while still remaining approachable."

"I worked with Judge Richards for so many years, and regardless of who was involved, or how it panned out in the courtroom, he always treated everyone with dignity and respect," says Faribault County's victim witness coordinator Deb Weiderhoft. "The loss of Judge Richards is a great one that can be felt throughout the community."

Before his death, Judge Richards spent many years participating in the local Relay For Life event. In 2017, the Faribault County Register had the opportunity to speak with him about his battle with cancer.

"The best thing in life is to keep a positive focus on things," Richards told the Register. "There's no need to think negative thoughts, stay positive. Keeping positive is not going to cure your disease, but it will give you better days, and it is important to make every day count."

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Doug Richards remembered - faribaultcountyregister.com | News, Sports, Information on the Blue Earth region - Faribault County Register

Kadimastem Finishes Treating Second Group of ALS Patients with AstroRx in Phase 1/2a Trial – ALS News Today

Kadimastem has finished treating its second group of participants in a Phase 1/2a clinical trial testing the safety and preliminary efficacy of AstroRx, aninvestigational stem cell therapy for amyotrophic lateral sclerosis (ALS).

AstroRx is an off-the-shelf cell therapy consisting of fully mature astrocytes star-shaped cells derived from human embryonic stem cells that are injected into the fluid surrounding the spinal cord to support damaged motor neurons.

Astrocytes usually help maintain a healthy environment in the brain, but often malfunction in ALS, contributing to disease progression. AstroRx was designed to compensate for diseased astrocytes and prevent the loss of motor nerve cells. The therapys goal is to potentially slow disease progression, improve quality of life, and extend life expectancy.

The U.S. Food and Drug Administration grantedAstroRx orphan drug status in November 2018 for the treatment of ALS, a designation meant to accelerate the development of AstroRx for this rare condition.

Earlier preclinical studiesshowed that AstroRx delayed disease onset, maintained muscle function, and prolonged survival in mice and rat models of ALS. The treatment also was found to be safe, with no signs of toxicity.

The ongoing, open-label, Phase 1/2a trial (NCT03482050) is testing the safety and preliminary signs of efficacy of AstroRx in people with ALS. Underway at the Hadassah Ein-Kerem Medical Center in Israel, the trial is expected to enroll 21 patients, ages 18-70, with early stage disease. Recruitment is ongoing.

The trial was originally designed to test three doses of AstroRx delivered into the spinal canal: a low dose of 100 million cells, a medium dose of 250 million cells, and a high dose with two consecutive administrations of 250 million cells.

However, after promising early efficacy results from the low-dose group (cohort A), Kadimastem is seeking to amend the trial protocol. It wants the third group of patients (cohort C) to receive two consecutive injections of the low dose, instead of the originally planned medium dose. Pending positive safety and efficacy results from the first three cohorts, a fourth group (cohort D) will receive two injections of the medium dose.

Safety and tolerability are the studys primary outcome measures. Secondary goals include changes in patients ALS Functional Rating Scale revised (ALSFRS-R) scores, respiratory muscle strength, hand grip strength, limb muscle strength, and quality of life.

In cohort A, the low-dose group, the therapy was found to be safe, with no serious side effects or dose-limiting toxicities. Participant had increased ALSFRS-R scores in the three months after treatment, suggesting a gain in functional abilities.

The trial has now treated all five ALS patients in cohort B, the second group, with the medium dose. Participants will be monitored for six months to evaluate the therapys safety and preliminary efficacy. The company expects to report the results for this group in August 2020.

Completing treatment for the additional 5 ALS patients in Cohort B, for a total of 10 patients treated with our product in our clinical trial, serves as an additional demonstration of our ability to develop and produce high quality clinical grade cells and takes us a significant step forward in our path to bringing innovative cure to ALS, Rami Epstein, CEO of Kadimastem, said in a press release.

The expected completion of cohort B 6-months follow-up period will allow us to assess the safety and preliminary efficacy of [250 million]cells, compared to that of the lower dose administered in cohort A, he added.

Kadimastem has recruited the first patient of cohort C, who all will receive two AstroRx injections of 100 million cells, separated by 2-3 months. Results from this group are expected during the first half of 2021.

The results of the next treatment group, Cohort C, in which each patient will be treated with two consecutive injections separated by an interval of 2-3 months, will allow us to assess the possible prolonged efficacy of the repeated dose, compared to the single dose treatment provided in cohorts A and B, said Michel Revel, founder and chief scientific officer of Kadimastem.

The results that will be obtained from the different cohorts, will support us in the process of defining the dose and treatment regimen that will lead to most favorable results for patients over time, Revel said.

Alejandra has a PhD in Genetics from So Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.

Total Posts: 6

Ins holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Cincias e Tecnologias and Instituto Gulbenkian de Cincia. Ins currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.

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Kadimastem Finishes Treating Second Group of ALS Patients with AstroRx in Phase 1/2a Trial - ALS News Today

Jasper Therapeutics Announces Expansion of Series A Financing, Bringing Total Corporate Fundraising to More than $50 Million – Business Wire

PALO ALTO, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced the expansion of its Series A financing with an additional investment of $14.1 million led by Roche Venture Fund and with participation from other investors, bringing the total company financing to more than $50 million to date. The initial Series A round was led by Abingworth LLP and Qiming Venture Partners USA, with further investment from Surveyor Capital (a Citadel company) and participation from Alexandria Venture Investments, LLC.

Jasper plans to use the proceeds to advance and expand the study of its lead clinical asset, JSP191. A humanized antibody targeting CD117 on hematopoietic stem cells, JSP191 is designed to replace toxic chemotherapy and radiation therapy as conditioning regimens to prepare patients for curative stem cell and gene therapy. JSP191 is the only antibody of its kind in clinical development as a single conditioning agent for people undergoing curative hematopoietic cell transplantation.

This investigational agent is currently being evaluated in a Phase 1/2 dose-escalation and expansion study as a conditioning agent to enable stem cell engraftment in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that resulted in poor outcome. Initial positive results from this ongoing clinical trial were presented in an oral session at the American Society of Hematology (ASH) Annual Meeting in December 2019. Jasper plans to expand the Phase 1/2 clinical study to include patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) receiving hematopoietic cell transplant. The development of JSP191 is supported by a collaboration with the California Institute for Regenerative Medicine (CIRM).

About Hematopoietic Cell TransplantationBlood-forming, or hematopoietic, stem cells are rare cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow by transplantation and engraftment of healthy stem cells is the only cure for most of these life-threatening conditions. Successful transplantation is currently achieved by subjecting patients to toxic treatment with radiation and/or chemotherapy followed by transplantation of a donor or gene-corrected hematopoietic cell graft. These toxic regimens cause DNA damage and lead to short- and long-term toxicities, including unwanted damage to organs and prolonged hospitalization. As a result, many patients who could benefit from a hematopoietic cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant. IND-enabling studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper TherapeuticsJasper Therapeutics is a biotechnology company focused on hematopoietic cell transplant therapies. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at https://jaspertherapeutics.com.

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Jasper Therapeutics Announces Expansion of Series A Financing, Bringing Total Corporate Fundraising to More than $50 Million - Business Wire

Global Stem Cell Therapies Overview Report 2019: The Highs & Lows, Off-The-Shelf Solutions, New Technologies, and Safety, Efficacy & Logistical…

DUBLIN, Jan. 8, 2020 /PRNewswire/ -- The "Highs and Lows of Stem Cell Therapies: Off-The-Shelf Solutions" report has been added to ResearchAndMarkets.com's offering.

The report includes:

Key Topics Covered

Chapter 1 Sources and Characteristics of Stem Cells

Chapter 2 New Technologies Driving Stem Cell Development

Chapter 3 Safety, Efficacy and Logistical Challenges

Chapter 4 Off-the-Shelf Solutions

Chapter 5 Companies and Technologies to Watch

Chapter 6 References

List of TablesTable 1: Stem Cell SourcesTable 2: Comparison of Stem CellsTable 3: Stem Cell Types Versus Cell PropertiesTable 4: Recent Advances in Genome Modulation TechnologiesTable 5: FDA-Approved Cell-Based TherapiesTable 6: Acute and Delayed Adverse Events Associated with Proven and Unproven Stem Cell-Based InterventionsTable 7: Companies Leading the Field in Cell-Based Therapies

List of FiguresFigure 1: Stem Cell Sources Figure 2: Two-Dimensional Versus Three-Dimensional Cell CultureFigure 3: Schematic of Approaches Used for Three-Dimensional Stem Cell Culture Figure 4: Patient Management Strategies to Decrease Side Effects Related with CAR-T Cell Therapy

For more information about this report visit https://www.researchandmarkets.com/r/15o8p9

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Research and Markets Laura Wood, Senior Manager press@researchandmarkets.com

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SVC112 molecule reduces effects of cancer stem cells with little toxicity – Drug Target Review

A study has shown that the SVC112 molecule can prevent cancer stem cells from producing more tumour cells in cell lines and mice, with no impact on healthy cells.

Researchers have found that SVC112, a molecule based on the chemical bouvardin, can act specifically against head and neck cancer stem cells (CSCs).

Bouvardin can be extracted from the Bouvardia ternifolia bush, native to Central America. Research from the University of Colorado, US has previously shown that bouvardin can slow a cancers ability to make proteins which allow it to grow and metastasise.

As CSCs manufacture cells that become the bulk of cancer tissue, they are a viable drug target. However, they often resist treatments like radiation and chemotherapy.

when the population of stem cells was reduced to under one percent of the tumour cells, the tumour began to shrink

The current study, conducted by scientists at SuviCa, synthesised SVC112 in order to control tumours more effectively than current FDA-approved protein synthesis inhibitors and with less toxicity.

The groups work showed that SVC112 acts specifically against proteins like Myc and Sox2 which are required by CSCs, while leaving healthy cells unharmed. They demonstrated this by comparing the effects of the drug in matched pairs of cancer cells and healthy cells grown from samples donated by five head and neck cancer patients.

Many groups have linked the production of transcription factors to the survival and growth of CSCs, but inhibitors have just been too toxic they come with too many side effects. Definitely our studies suggest that this drug could be an advantage over existing drugs. It inhibits protein synthesis in a way that no other drug does and thats why were excited, says lead researcher Dr Tin Tin Su.

For further comparison, the researchers conducted the same experiment with the FDA-approved protein synthesis inhibitor omacetaxine mepesuccinate (also called homoharringtonin, or HHT).

Having cancer cells along with matched non-cancer cells from the same patient is pretty unique. When we tested these matched pairs with SVC112 and with HHT, what we saw is the approved drug eliminated both cancer and normal cells, whereas SVC112 had selectivity it affected cancer cells but not healthy cells so theoretically the effects on the normal tissue will be less, Su says.

Next, the team used SVC112 to treat head and neck tumours in mouse models, grown from samples of human tumours. Earlier work showed that SVC112 sensitised previously radiation-resistant CSCs to radiation treatment, so the group tested the molecule and radiation alone and in combination.

They found that when the population of stem cells was reduced to under one percent of the tumour cells, the tumour began to shrink. They concluded that the CSCs act as controllers for the growth of tumours, so impairing this group of stem cells will slow down or stop cancer.

The researchers hope that their pre-clinical results will lay the groundwork for human clinical trials of SVC112 in head and neck cancer patients.

The findings were published in Cancer Research.

Excerpt from:
SVC112 molecule reduces effects of cancer stem cells with little toxicity - Drug Target Review

Q&A: Cancer Death Rates Are Falling Nationally. Here’s What’s Happening at UVA – University of Virginia

This week, the American Cancer Society released some very welcome news: the cancer death rate in the U.S. dropped by 2.2% from 2016 to 2017, the largest single-year drop ever recorded.

The drop, which the report attributes to plummeting smoking rates as well as new screening and treatment methods, continues a decades-long trend, as cancer death rates have fallen by nearly 30% since 1991 about 2.9 million fewer deaths.

Dr. Thomas Loughran, director of the University of Virginia Cancer Center, said UVA is in step with this national trend.

The UVA Cancer Center is one of 71 National Cancer Institute-designated treatment centers nationwide and ranked among the nations top 50 cancer centers over each of the past four years (No. 26 last year). The center serves approximately 4 million people in Virginia and West Virginia.

We spoke with Loughran about what he is seeing at UVA and beyond, new treatments and research helping to eradicate cancer, and where he sees cancer treatment in five years.

Q. Why have cancer death rates dropped so significantly?

A. As reports of this latest drop have said, a large part of the decline can be attributed to declining rates of lung cancer. The importance of preventing cancer particularly behavioral interventions like stopping smoking has become more prominent, and there have been remarkable declines in smoking across the United States.

This is a very important focus for us at UVA. We serve a large geographical area 90 contiguous counties in Virginia and West Virginia, including rural Appalachia. Southwest Virginia in Appalachia still has high smoking rates, and as a result, high rates of lung cancer. Education, screening and tobacco cessation programs are critically important, especially in those areas.

Q. What advances in treatment have contributed to falling cancer death rates, nationally and at UVA?

A. Screening technology, especially for the more common cancers like lung, colorectal, prostate and breast cancer, has improved. The latest report probably doesnt fully reflect recent implementation of lung cancer screening using a low-dose CT scan, recommended for high risk individuals and especially those with a history of heavy smoking. That has only been around a few years, and its impact will likely show up in future reports.

The second big factor is the development of immunotherapy [cancer treatments that utilize and help the patients immune system]. UVA has invested quite a lot of institutional resources in becoming a state-of-the-art immunotherapy center, and I am proud to say we are a leader in the field.

We have created a Cancer Therapeutics Program to support the development of new therapies. Dr. Craig Slingluff, who leads that program, is a surgical oncologist internationally famous for immunotherapy treatments for melanoma. To strengthen this program, we have recruited a cadre of leading physician scientists from across the country. Dr. Karen Ballen came here to lead our stem cell and bone marrow transplant program. Dr. Lawrence Lum, the scientific director of the transplant program, has developed a novel therapy using antibodies that bind to both T-cells [patient cells that can kill cancer cells] and tumor cells, forming a bridge between the two that helps the T-cells kill the cancer cells. Dr. Trey Lee is a leader in CAR-T cell therapy.

I could keep going; there are so many great people working on this. We also have a new Good Manufacturing Practice lab, supported by a grant from the commonwealth, that will help us grow and modify T-cells as needed and give them to patients under sterile conditions. That just opened and we are very excited about that program.

Q. What other areas of research have shown great promise?

A. Some of our work in nanotechnology is really unique and exciting. [Biomedical engineering professor] Mark Kester directs UVAs nanoSTAR Institute, which is working on delivering cancer therapies by nanotechnology basically, engineering at a very small scale. For example, nanoliposomes a sort of delivery system for cancer therapy are actually smaller than individual cells and can therefore penetrate cancer cells and release treatment from inside those cells.

We are very excited about early phase trials testing this technology on solid tumors, and we also hope to use it to treat patients with acute leukemia over the next few years.

Q. Looking ahead, where do you see the next big gains coming from?

A. Immunotherapy has revolutionized cancer treatment, but why some patients respond well and some dont remains puzzling. I hope that we can begin to discover why some patients are reacting to these newer treatments differently than others. Once we figure out why some patients respond to immunotherapy, we can begin to make improvements that could benefit a larger percentage of patients with these deadly cancers.

CAR T Cell therapy one method of immunotherapy is very effective against leukemia, lymphoma and cancers of the blood, but not yet against solid tumors. Over the next five years, I hope we can determine how to deliver these T-cells to solid tumors such as those found in lung, colorectal and other common cancers again to make this advance more widely applicable to a larger number of patients.

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Q&A: Cancer Death Rates Are Falling Nationally. Here's What's Happening at UVA - University of Virginia