Stem Cell Clinic

Nivolumab Shows Significant Benefit for Hodgkin's Lymphoma in Mayo Clinic Co-Led Phase I Study

By Stem Cell Clinic

Released: 5-Dec-2014 11:00 AM EST Embargo expired: 6-Dec-2014 1:00 PM EST Source Newsroom: Mayo Clinic Contact Information

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Nivolumab shows significant benefit for Hodgkin’s lymphoma in Mayo Clinic co-led phase I study

Newswise A phase I clinical trial of nivolumab found that the immune-boosting drug is a highly effective therapy for Hodgkins lymphoma. The multi-institution study, led by Mayo Clinic, indicated that the drug was safe and led to an 87 percent response rate in patients who had failed on other treatments. Results of the study appear in the New England Journal of Medicine.

The findings support further development of nivolumab, which enhances the immune systems ability to detect and kill cancer cells. The drug has already demonstrated benefit in the treatment of other cancers, particularly melanoma, renal cell cancer, lung cancer and bladder cancer.

Nivolumab is a very promising agent that is reasonably well-tolerated and can easily be combined with other agents in the future, says Stephen Ansell, M.D., Ph.D., a hematologist and co-lead author of the study. There is evidence now that you can fight cancer by optimizing your immune function, either by enhancing signals that stimulate the immune response or blocking signals that dampen it.

The immune systems T cells are specifically trained to fight infectious diseases and cancer. When these cells are called to active duty, their extracellular armor is marked with an immune checkpoint protein, a type of off switch called PD1 that can be used to shut down the immune response. Other immune cells carry molecular keys or ligands named PD-L1 or PD-L2, which can flip that switch to protect normal tissues from collateral damage.

Cancer cells can co-opt this PD-1 pathway by making their own copy of the keys and using them to turn off T cells before they attack. The malignant cell in Hodgkins lymphoma, the Reed-Sternberg cell, has very high levels of PD-L1 and PD-L2 on its cell surface. Therefore, Dr. Ansell and his colleagues hypothesized that using the known immune checkpoint inhibitor nivolumab to block PD1 could prevent these malignant cells from evading immune detection.

In the phase I study, the researchers gave nivolumab every two weeks to 23 patients with relapsed or refractory Hodgkin's lymphoma who were heavily pretreated. The drug appeared to be safe at its highest doses of 3 mg/kg, with rash and decreased platelet counts being the most common drug-related adverse events.

The researchers observed substantial therapeutic activity, with an objective response rate of 87 percent. Seventeen percent of patients had complete responses and 70 percent had partial responses. Progression-free survival at 24 weeks was 86 percent; 11 patients are still in the study. Six patients discontinued participation because of stem-cell transplantation, four because of disease progression, and two because of drug toxicity.

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Nivolumab Shows Significant Benefit for Hodgkin's Lymphoma in Mayo Clinic Co-Led Phase I Study

Vast Majority of Life-Saving Cord Blood Sits Unused

By Stem Cell Doctors

High costs keep patients from using stem cells harvested from umbilical cords

Scientists are studying ways to treat HIV, cerebral palsy and other diseases using umbilical cord blood, although little of the collected blood will actually be used. Credit:Banc de Sang via flickr

Youd think doctors and patients would be clamoring for cells so versatile they could help reboot a body suffering from everything from leukemia to diabetes. But a new report shows that an important source of these stem cellsdiscarded umbilical cordsis rarely used because of high costs and the risk of failure.

Stem cells drawn from newborns umbilical cord blood are sometimes used to treat medical conditions, especially bone and blood cancers like multiple myeloma or lymphoma by replacing dysfunctional blood-producing cells in bone marrow. Generally the diseased cells are destroyed with chemotherapy and irradiation. Then new stem cells are transplanted into the patient to restore function. Cord blood stem cells are an alternative to bone marrow transplants and peripheral blood transplants, in which stem cells are gathered from the blood stream. Cord blood tends to integrate better with the body and it is easier to find a suitable donor than the alternatives.

Yet less than 3 percent of cord blood collected in the U.S. is ever used whereas the rest sits uselessly in blood banks, according to a recent report in Genetic Engineering & Biotechnology News. Immunologist Enal Razvi is author of the report and managing director of Select Biosciences, a biotechnology consulting agency. Razvi found that public cord blood banks, which store donated frozen units for transplants as needed, have only a 1 to 3 percent turnover annually. Most of their inventory sits unused year after year. For example, at Community Blood Services in New Jersey, patients have only used 278 of its 13,000 cords since it opened in 1996, according to business development director Misty Marchioni. Usage is even lower at private cord blood banks, which charge clients thousands of dollars to store a cord in the event a family member one day needs it.

Unlike bone marrow, the main alternative stem cell source, cells transplanted from cord blood carry little risk of graft-versus-host disease, a deadly condition in which the body rejects a transplant. Scientists believe this is because a babys immune system is closer to a blank slate, so their stem cells can integrate with the patients body more easily. But cord blood transplants also take longer to start working, requiring longer hospital stays and upping the bill. Due to storage and testing costs, the cords themselves also get pricy. The cost of the cord is prohibitively high, Razvi explains. Each unit of cord blood costs between $35,000 and $40,000 and most adults require two units for a successful transplant. Insurance companies will generally pay a set amount for a stem cell transplant regardless of where the cells come from. The price tag on a cord blood transplant can run up to $300,000, which may not be fully covered.

Cord blood stem cell transplants also have a higher failure rate than other transplant methods. If the transplant fails, it leaves patients with a compromised immune system in addition to their original disease and medical bills. Because the preparation for transplant includes wiping out the patients original bone marrow, the entire body has to be repopulated with stem cells able to replace it. There are not many stem cells in each cord. Compared with bone marrow or peripheral blood there is a greater chance that there will not be enough stem cells that actually implant and begin producing blood and bone marrow. Its like spreading a small amount of seeds in a big garden, says Mitchell Horwitz, who teaches cell therapy at Duke University Medical Center. Sometimes it just doesnt take.

Martin Smithmyer, chief executive of the private bank Americord, claims that more clients will eventually use their cords, especially as more applications are found for cord blood stem cells. But some scientists disagree. Steven Joffe, a professor of medical ethics at the University of Pennsylvania Perelman School of Medicine, says that many treatments cannot be done with a patients own stem cells because genetic diseases would already be present in the cord blood and that bone marrow might be a better option for relatives. The likelihood they are ever going to use that product is vanishingly small, he says.

Despite the low usage, advocates say cord blood programs have been crucial in improving transplant options for racial minorities, because it can be hard to find a bone marrow match for some groups. Cord blood does not need to match the patient as perfectly as bone marrow. This has transformed the treatment of minority patients, says Andromachi Scaradavou, medical director of the National Cord Blood Program, a public bank based in New York City. In the past we didnt have good donors to offer them. Community Blood Servicess Marchioni also maintains that cord blood is a good emergency option, because finding a compatible bone marrow or peripheral blood donor can take months or years. If you need a transplant quickly, she says, its easy to get cord blood off of a shelf.

Still, experts are working on more efficient ways of ensuring widespread availability of cord blood without having so much of it sit forever unused. Researchers are also continuing to look for ways to improve transplant success and to increase the number of stem cells obtained from each cord, potentially bringing down costs and making cord blood transplants feasible for more patients. If the cost could be lowered, Scaradavou says, it would help a lot of patients get the treatment they need.

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Stem Cells from Adult Nose Tissue Used to Cure Parkinsons Disease in Rats

By Stem Cell Medicine

Durham, NC (PRWEB) December 05, 2014

Scientists have for the first time used adult human stem cells to cure rats with Parkinsons disease, a neurodegenerative illness that currently has no cure. The study, published in the current issue of STEM CELLS Translational Medicine, details how a team of researchers working in Germany at the University of Bielefeld (UB) and Dresden University of Technology were able to produce mature neurons using inferior turbinate stem cells (ITSCs).

ITSCs are stem cells taken from tissue that would generally be discarded after an adult patient undergoes sinus surgery.

The team then tested how the ITSCs would behave when transplanted into a group of rats with Parkinsons disease. Prior to transplantation, the animals showed severe motor and behavioral deficiencies. However, 12 weeks after receiving the ITSCs, the cells had migrated into the animals brains and functional ability was not only fully restored, but significant behavioral recovery was witnessed, too. In another positive sign, no tumors were found in any of the animals after the transplantations, something that also has been a concern in stem cell therapy.

Due to their easy accessibility and the resulting possibility of an autologous transplantation approach, ITSCs represent a promising cell source for regenerative medicine, said UBs Barbara Kaltschmidt, Ph.D., who led the study along with Alexander Storch, M.D., and Christiana Ossig, M.D., both of Dresden University. The lack of ethical concerns associated with human embryonic stem cells is a plus, too.

In contrast to fighting the symptoms of Parkinsons disease with medications and devices, this research is focused on restoring the dopamine-producing brain cells that are lost during the disease, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "These cells are easy to access and isolate from nasal tissue, even in older patients, which adds to their attraction as a potential therapeutic tool.

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The full article, Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in Parkinsonian rats can be accessed at http://www.StemCellsTM.com.

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Stem Cells from Adult Nose Tissue Used to Cure Parkinsons Disease in Rats

Use of Unproven Stem Cell Therapy Questioned

By Stem Cell Treatment

Robert Vondracek has had multiple sclerosis for 20 years. His speech is starting to slur and he's been having more trouble getting around, and when he heard about a controversial stem cell therapy that might help, he got excited.

"I heard about the stem cell treatments being done right here in Phoenix," said Vondracek, 61. "It shocked me because it was not approved in this country, I didn't think."

The therapy was offered by an Arizona plastic surgeon who gives the stem cell treatments in the same clinic where he does cosmetic procedures.

But when Vondracek's neurologist heard about his interest in the therapy, which would cost $7,000 per treatment, "He went crazy," said Vondracek. He strongly advised Vondracek against it.

Plastic surgeons, other doctors and naturopaths at more than 100 clinics round the country are charging thousands of dollars for a controversial procedure called stem cell therapy to treat a range of disorders, including neurological diseases like MS and Parkinson's.

Robert Vondracek and his girlfriend, Terese Knapik.

The procedure has angered many neurologists and prominent researchers who say these doctors are preying on vulnerable people and capitalizing on the huge but still unrealized potential of stem cell research, which they say is years away from producing an approved treatment for neurological diseases.

"Peddling snake oil in the guise of stem cell therapies is really a threat to legitimate research," said Dr. George Daley, director of the Stem Cell Transplantation Program at Boston Children's Hospital, past president of the International Society for Stem Cell Research and a professor at Harvard Medical School.

"Finding cures is hard, it takes sometimes decades, it's extremely expensive and it's not something that we can just wish and hope for," he said. "It can only be achieved through very, very hard work."

Dr. George Daley is a nationally recognized expert on stem cells at Boston Childrens Hospital and Harvard Medical School.

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Cordlife launches newly upgraded stem cell facility

By Stem Cell Treatment

Cordlife Medical Philippines Inc. (Cordlife), a fully owned subsidiary of Cordlife Group Ltd., a Singapore Exchange mainboard-listed consumer healthcare company catering to the mother and child segment, recently opened its newly upgraded stem cell processing and cryopreservation facility at UP-Ayalaland Technohub in Quezon City.

This expansion came less than five years from the opening of its facility in the country and was mainly driven by the growing number of parents who recognize the value of banking here their babys stem cells.

The event launch held at Crowne Plaza in Ortigas was hosted by popular DJ Delamar Arias and graced by celebrity moms, actress and beauty queen Lara Quigaman and journalist Nia Corpuz. Delamar, Lara and Nia all shared their personal experiences of being Cordlife moms themselves.

Also in attendance to underscore Cordlifes commitment to Filipino parents and their children were Cordlife Group CEO Jeremy Yee, Cordlife Philippines medical director Dr. Arvin Faundo and Cordlife Philippines director Michael Arnonobal.

The event highlighted the five essentials of mother and child that Cordlife addresses through services. These essentials are security, expertise, investment, bond and value for life.

With the newly upgraded stem cell facility that can accommodate up to 30,000 cord blood and cord lining units, more parents can enjoy a sense of security when they bank their babys stem cells at Cordlifes state-of-the-art processing and cryopreservation laboratory.

Peace of mind

Those who banked with Cordlife can have peace of mind knowing that their babys stem cells are kept in a highly-secure laboratory that was built to withstand earthquakes of up to magnitude 8, and ward off fire with its fire-retardant walls. Furthermore, the vapor-phased liquid nitrogen cryogenic tanks used to preserve the cord blood and cord lining samples are not dependent on electricity, making them 100-percent safe and reliable in case of power outages.

Cordlifes expertise in the stem cell banking arena, is proven not only by being the largest network of cord blood banks in Asia, but also the number of cord blood releases for stem cell transplant and their adherence to the stringent global standards of AABB (formerly known as American Association of Blood Banks).

Cordlife Philippines is also the countrys first and only ISO 9001:2008 and Department of Health-registered cord blood and cord lining bank.

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Cordlife launches newly upgraded stem cell facility

Uniting the Global Stem Cell Community

By Stem Cell Treatment

Posted by Dana Sparks (@danasparks) 3 day(s) ago

Uniting the Global Stem Cell Community

The World Stem Cell Summit, December 3-5 in San Antonio, unites and educates the global stem cell community. With more than 1,200 attendees from more than 40 countries, the annual World Stem Cell Summits interdisciplinary agenda explores disease updates, research directions, cell standardization, regulatory pathways, reimbursements, financing, venture capital and economic development.

Throughout the week, the Mayo Clinic Center for Regenerative Medicine will use social media to connect using the hashtag #WSCS14. At the end of the week, we'll let the tweets, Google+ posts, Flickr photos, Facebook posts and YouTube videos tell the story.

The World Stem Cell Summit includes in-depth programming and more than 200 international speakers, including leaders from theMayo Clinic Center for Regenerative Medicine:

About the World Stem Cell SummitMayo Clinic, The University of Texas Health Science Center at San Antonio, Kyoto University Institute for Integrated Cell-Material Sciences (iCeMS), BioBridge Global, Baylor College of Medicine and the Regenerative Medicine Foundation have joined the Genetics Policy Institute to organize the10th Annual World Stem Cell Summit the largest and most comprehensive multi-track interdisciplinary stem cell conference.

Related LinksMayo Clinic at World Stem Cell Summit 2013Mayo Clinic at World Stem Cell Summit 2012

Regenerative MedicineWorld Stem Cell Summit

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Uniting the Global Stem Cell Community

The Adult Stem Cell Technology Center, LLCs New Report on Asymmetric Character of Stem Cell Chromosomes Advances …

By Stem Cell Medicine

Boston, MA (PRWEB) December 04, 2014

In a new report published in the online journal Cell Death and Disease, the Adult Stem Cell Technology Center, LLC (ASCTC) continues to demonstrate its special expertise in uncovering unknown properties that are unique to adult tissue stem cells. In particular, the new study continues to build the companys portfolio of technologies that make previously invisible adult stem cells not only identifiable, but also countable.

The studies were performed with mouse hair follicle stem cells. Because of the universal nature of adult tissue stem cell properties, the new findings are predicted to apply to stem cells in a wide range of human tissues as well.

For the past half century since the experimental demonstration of their existence, it has not been possible to identify adult tissue stem cells exclusive of other related cell types. Consequently, counting them has been impossible, too. Established stem cell therapies like bone marrow transplantation are suboptimal because of this limitation; and the current worldwide flood of thousands of clinical trials of tissue stem cell transplantation therapies has the same problem. Without being able to count potentially curative adult tissue stem cells, there is no way to optimize and standardize successful treatments.

The new report presents a discovery made during studies employing one of the ASCTCs recently defined biomarkers for detecting tissue stem cells. The new biomarker is a member of a family of cell factors called histones that package the cellular DNA into chromosomes. One of the less abundant members of this family is called H2A.Z. In 2011, the ASCTC discovered that H2A.Z is only accessible on the set of chromosomes that segregates to the stem cell sister when a stem divides to produce a non-stem sister cell. The non-stem sister differentiates to replenish lost mature tissue cells. Before a stem cell divides in this manner, the stem cell chromosomes and the non-stem cell chromosomes are distinct because of this difference in their H2A.Z access. This unique feature, called H2A.Z asymmetry, is a highly specific biomarker for identifying adult tissue stem cells.

Because detection of H2A.Z asymmetry does not disrupt other features of stem and non-stem chromosomes, it can be used as a specific landmark to discover other molecular differences between chromosomes destined for the stem cell sister and chromosomes destined for the non-stem sister. The new report describes how two well-known gene regulation modifications of an abundant histone family member, H3, also display asymmetry between stem cell chromosomes and differentiating cell chromosomes.

The newly discovered asymmetric chromosomal patterning of gene regulation modifications in adult tissue stem cells may reveal a long sought mechanism to explain how stem cell fate is maintained in mammalian tissues. This new insight into the function of tissue stem cells addresses a fundamental question in the field of stem cell biology research. ASCTC Director James L. Sherley anticipates that the new report will give stem cell scientists and bioengineers a new lead idea and new research tools for extending knowledge on the molecular workings of adult tissue stem cells. Such advances in knowledge are greatly needed currently to improve the scientific foundation for the increasing number of regenerative medicine clinical trials.

******************************************************************************************** The Adult Stem Cell Technology Center, LLC is a Massachusetts life sciences company. ASCTC Director and founder, James L. Sherley, M.D., Ph.D. is the foremost authority on the unique properties of adult tissue stem cells. The companys patent portfolio contains biotechnologies that solve the three main technical problems production, quantification, and monitoring that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells. Currently, ASCTC is employing its technological advantages to pursue commercialization of facile methods for monitoring adult tissue stem cell number and function.

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The Adult Stem Cell Technology Center, LLCs New Report on Asymmetric Character of Stem Cell Chromosomes Advances ...

Global Stem Cells Group Hands-on Training Course in Barcelona Heading to Additional Euro Cities in 2015

By Stem Cell Medicine

MIAMI (PRWEB) December 04, 2014

After a successful first run in Spain last month, Global Stem Cells Group, has announced the decision to take the biotech companys hands-on stem cell training course to additional European cities in 2015. GSCG subsidiary Stem Cell Training, Inc. and Dr. J. Victor Garcia conducted the Adipose Derived Harvesting, Isolation and Re-integration Training Course for medical professionals in Barcelona Nov. 22-23, 2014.

The two-day, hands-on intensive training course was developed for physicians and high-level practitioners to learn techniques in harvesting and reintegrating stem cells derived from adipose tissue and bone marrow. The objective of the training is to bridge the gap between bench science in the laboratory and the doctors office by teaching effective, in-office regenerative medicine techniques.

Global Stem Cells Group will release a schedule of cities and dates for future training classes in upcoming weeks.

For more information, visit the Stem Cell Training, Inc. website, email info(at)stemcelltraining(dot)net, or call 305-224-1858.

About Global Stem Cells Group: Global Stem Cells Group, Inc. is the parent company of six wholly owned operating companies dedicated entirely to stem cell research, training, products and solutions. Founded in 2012, the company combines dedicated researchers, physician and patient educators and solution providers with the shared goal of meeting the growing worldwide need for leading edge stem cell treatments and solutions.

With a singular focus on this exciting new area of medical research, Global Stem Cells Group and its subsidiaries are uniquely positioned to become global leaders in cellular medicine.

Global Stem Cells Groups corporate mission is to make the promise of stem cell medicine a reality for patients around the world. With each of GSCGs six operating companies focused on a separate research-based mission, the result is a global network of state-of-the-art stem cell treatments.

About Stem Cell Training, Inc.:

Stem Cell Training, Inc. is a multi-disciplinary company offering coursework and training in 35 cities worldwide. Coursework offered focuses on minimally invasive techniques for harvesting stem cells from adipose tissue, bone marrow and platelet-rich plasma. By equipping physicians with these techniques, the goal is to enable them to return to their practices, better able to apply these techniques in patient treatments.

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Global Stem Cells Group Hands-on Training Course in Barcelona Heading to Additional Euro Cities in 2015

New single-cell analysis reveals complex variations in stem cells

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: Kat J. McAlpine katherine.mcalpine@wyss.harvard.edu 617-432-8266 Wyss Institute for Biologically Inspired Engineering at Harvard @wyssinstitute

(BOSTON) -- Stem cells offer great potential in biomedical engineering due to their pluripotency, which is the ability to multiply indefinitely and also to differentiate and develop into any kind of the hundreds of different cells and bodily tissues. But the precise complexity of how stem cell development is regulated throughout states of cellular change has been difficult to pinpoint until now.

By using powerful new single-cell genetic profiling techniques, scientists at the Wyss Institute for Biologically Inspired Engineering and Boston Children's Hospital have uncovered far more variation in pluripotent stem cells than was previously appreciated. The findings, reported today in Nature, bring researchers closer to a day when many different kinds of stem cells could be leveraged for disease therapy and regenerative treatments.

"Stem cell colonies contain much variability between individual cells. This has been considered somewhat problematic for developing predictive approaches in stem cell engineering," said the study's co-senior author James Collins, Ph.D., who is a Wyss Institute Core Faculty member, the Henri Termeer Professor of Medical Engineering & Science at MIT, and a Professor of Biological Engineering at MIT. "Now, we have discovered that what was previously considered problematic variability could actually be beneficial to our ability to precisely control stem cells."

The research team has learned that there are many small fluctuations in the state of a stem cell's pluripotency that can influence which developmental path it will follow.

It's a very fundamental study but it highlights the wide range of states of pluripotency," said George Daley, study co-senior author, Director of Stem Cell Transplantation at Boston Children's Hospital and a Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. "We've captured a detailed molecular profile of the different states of stem cells."

Taking this into account, researchers are now better equipped to manipulate and precisely control which cell and tissue types will develop from an individual pluripotent stem cell or stem cell colony.

"The study was made possible through the use of novel technologies for studying individual cells, which were developed in part by collaborating groups at the Broad Institute, giving our team an unprecedented view of stem cell heterogeneity at the individual cell level," said Patrick Cahan, co-lead author on the study and Postdoctoral Fellow at Boston Children's Hospital and Harvard Medical School.

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New single-cell analysis reveals complex variations in stem cells

Predicting the storm: Can computer models improve stem cell transplantation?

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PUBLIC RELEASE DATE:

4-Dec-2014

Contact: John Wallace wallacej@vcu.edu 804-628-1550 Virginia Commonwealth University @vcunews

Is the human immune system similar to the weather, a seemingly random yet dynamical system that can be modeled based on past conditions to predict future states? Scientists at VCU Massey Cancer Center's award-winning Bone Marrow Transplant (BMT) Program believe it is, and they recently published several studies that support the possibility of using next-generation DNA sequencing and mathematical modeling to not only understand the variability observed in clinical outcomes of stem cell transplantation, but also to provide a theoretical framework to make transplantation a possibility for more patients who do not have a related donor.

Despite efforts to match patients with genetically similar donors, it is still nearly impossible to predict whether a stem cell transplant recipient will develop potentially fatal graft-versus-host disease (GVHD), a condition where the donor's immune system attacks the recipient's body. Two studies recently published by the online journal Frontiers in Immunology explored data obtained from the whole exome sequencing of nine donor-recipient pairs (DRPs) and found that it could be possible to predict which patients are at greatest risk for developing GVHD and, therefore, in the future tailor immune suppression therapies to possibly improve clinical outcomes. The data provides evidence that the way a patient's immune system rebuilds itself following stem cell transplantation is representative of a dynamical system, a system in which the current state determines what future state will follow.

"The immune system seems chaotic, but that is because there are so many variables involved," says Amir Toor, M.D., member of the Developmental Therapeutics research program at Massey and associate professor in the Division of Hematology, Oncology and Palliative Care at the VCU School of Medicine. "We have found evidence of an underlying order. Using next-generation DNA sequencing technology, it may be possible to account for many of the molecular variables that eventually determine how well a donor's immune system will graft to a patient."

Toor's first study revealed a large and previously unmeasured potential for developing GVHD for which the conventional approach used for matching DRPs does not account. The conventional approach for donor-recipient compatibility determination uses human leucocyte antigen (HLA) testing. HLA refers to the genes that encode for proteins on the surface of cells that are responsible for regulating the immune system. HLA testing seeks to match DRPs who have similar HLA makeup.

Specifically, Toor and his colleagues used whole exome sequencing to examine variation in minor histocompatibility antigens (mHA) of transplant DRPs. These mHA are protein fragments presented on the HLA molecules, which are the receptors on cells' surface to which these fragments of degraded proteins from within a cell bind in order to promote an immune response. Using advanced computer-based analysis, the researchers examined potential interactions between the mHA and HLA and discovered a high level of mHA variation in HLA-matched DRPs that could potentially contribute to GVHD. These findings may help explain why many HLA-matched recipients experience GVHD, but why some HLA-mismatched recipients experience none remains a mystery. This seeming paradox is explained in a companion paper, also published in the journal Frontiers in Immunology. In this manuscript, the team suggests that by inhibiting peptide generation through immunosuppressive therapies in the earliest weeks following stem cell transplantation, antigen presentation to donor T cells could be diminished, which reduces the risk of GVHD as the recipients reconstitute their T-cell repertoire.

Following stem cell transplantation, a patient begins the process of rebuilding their T-cell repertoire. T cells are a family of immune system cells that keep the body healthy by identifying and launching attacks against pathogens such as bacteria, viruses or cancer. T cells have small receptors that recognize antigens. As they encounter foreign antigens, they create thousands of clones that can later be called upon to guard against the specific pathogen that presented the antigen. Over the course of a person's life, they will develop millions of these clonal families, which make up their T-cell repertoire and protect them against the many threats that exist in the environment.

This critical period where the patient rebuilds their immune system was the focus of the researchers' efforts. In previous research, Toor and his colleagues discovered a fractal pattern in the DNA of recipients' T-cell repertoires. Fractals are self-similar patterns that repeat themselves at every scale. Based on their data, the researchers believe that the presentation of minor histocompatability antigens following transplantation helps shape the development of T-cell clonal families. Thus, inhibiting this antigen presentation through immunosuppressive therapies in patients who have high mHA variation can potentially reduce the risk of GVHD by influencing the development of their T-cell repertoire. This is backed by data from clinical studies that show immune suppression soon after transplantation improves outcomes in unrelated DRPs.

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Predicting the storm: Can computer models improve stem cell transplantation?

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