Tag Archive for: Patrick Hanley

scientist working in a lab

Personalized T cell therapy for HIV shows safety and early signs of impact

scientist working in a lab

A new HIV-specific T cell therapy, tested in six adults living with HIV, used specially trained immune cells made from each person’s own blood — a personalized therapy designed to target the virus with precision.

An exciting small clinical trial led by the Center for Cancer and Immunology Research at Children’s National Hospital has shown that a new HIV-specific T cell therapy is safe and may help reduce hidden reservoirs of the virus in the body. This approach, tested in six adults living with HIV, uses specially trained immune cells made from each person’s own blood — a personalized therapy designed to target the virus with precision.

The results, published in Nature Communications, represent a step forward in the search for a long-term, drug-free way to control or even cure HIV.

A smarter way to fight HIV

Today, people living with HIV rely on anti-retroviral therapy (ART) to keep the virus under control. These medications are highly effective but must be taken daily and do not eliminate the virus entirely. That is because HIV can hide in a “reservoir” of cells where it remains dormant and invisible to both drugs and the immune system. If ART is stopped, the virus can quickly return.

To change that, scientists at Children’s National and partnering institutions developed a new type of cellular therapy called HST-NEETs — short for “HIV-specific T cells targeting conserved epitopes”. These T cells are trained in the lab to recognize parts of the virus that do not change much, even as HIV mutates. This makes it harder for the virus to escape. The goal is to help the immune system find and destroy the infected cells that are normally hidden.

Safe and promising results

In this phase 1 clinical trial, researchers created personalized HST-NEET therapy from each participant’s own immune cells. After training the cells to recognize HIV, they were infused back into the patients twice over a period of weeks.

The results showed that:

  • No serious side effects were reported from the infusions.
  • The treatment was well-tolerated by all six participants.
  • In two people, the therapy led to stronger HIV-specific immune responses, including more virus-fighting T cells and antibodies.
  • In two others, researchers saw a drop in the level of HIV hidden in their cells, a sign that the virus reservoir might be shrinking.
  • In four participants, the infused T cells persisted in the bloodstream for up to 40 weeks, continuing to patrol for signs of HIV.

While not a cure, these findings show early evidence that the therapy may help the body better recognize and fight HIV, even the hidden forms that are hardest to treat.

Building toward a cure

“The fact that we saw HIV-specific T cell responses increase in some participants, even without additional immune-boosting drugs, is very encouraging,” said Catherine Bollard, MBChB, MD, senior author of the study and director of the Center for Cancer and Immunology Research at Children’s National. “It suggests that the immune system can be trained to go after parts of the virus that were previously out of reach.”

Unlike bone marrow transplants, which have led to a cure in a few people with both HIV and cancer but carry high risk, HST-NEET therapy is much safer and more scalable. That is important for the millions of people living with HIV worldwide.

This study also sets the stage for future clinical trials that could combine T cell therapy with other strategies, like latency-reversing drugs that “wake up” hidden HIV, to further shrink the reservoir.  It also shows that personalized T cells can be safely made, infused and tracked over time and that they can continue working in the body for many months. Those lessons are valuable not just for HIV but also for developing safer, more targeted cancer immunotherapies in children and adults.

What’s next

The next phase of research will evaluate this therapy in larger groups and under different conditions, including in people undergoing stem cell transplants or with added immune system boosters. Clinical trials are already underway exploring these combinations.

By focusing on preserved parts of the virus, the regions that HIV cannot easily mutate, HST-NEETs could one day become part of a combination approach to eliminate HIV from the body altogether.

“Every step brings us closer to a functional cure,” said Dr. Bollard. “And the lessons we’re learning from HIV may also inform how we treat other chronic viral infections, and even cancer, in the future.”

Authors authors from Children’s National include Danielle K. Sohai, Michael D. Keller, Patrick J. Hanley, Fahmida Hoq, Divyesh Kukadiya, Anushree Datar, Emily Reynolds, Christopher Lazarski, Chase D. McCann, Jay Tanna, Abeer Shibli, Haili Lang, Anqing Zhang, Pamela A. Chansky, Cecilia Motta and Conrad Russell Y. Cruz.

Attendees at the 2nd annual Cell & Gene Therapy Symposium

Regional powerhouse: Cell and Gene therapy leaders from mid-Atlantic forge connections

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Nearly 200 biomedical leaders from Washington, D.C., Maryland, and Virginia gathered at the Children’s National Research & Innovation Campus for the 2nd annual Cell & Gene Therapy Symposium. The event showcased groundbreaking developments in rare disease treatments and underscored the importance of regional collaboration.

“By targeting diseases at the cellular level, we are on the cusp of breakthroughs in cell and gene therapy that will transform medicine,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research (CCIR) at Children’s National Hospital and a host of the symposium. “Progress will accelerate if we build partnerships beyond our own organizations.”

The big picture

Scientists and clinicians have worked for more than two decades to develop cell and gene therapies aimed at treating diseases on a cellular level. The past few years have been particularly promising as investment in science has led to advancements. Children’s National is at the forefront, as one of the first pediatric hospitals in the world to offer commercial gene therapies for sickle cell disease.

Many more treatments for rare diseases are in development at Children’s National and beyond. Leaders at CCIR are actively building collaborations with companies, academic institutions and enterprises across the mid-Atlantic region to accelerate these efforts.

During the symposium, Eugene Hwang, M.D., chief of Oncology at Children’s National, addressed the urgent need for more effective and less toxic treatments for pediatric brain tumors. He highlighted the potential of combining immunotherapies with innovations like low-intensity focused ultrasound, which can open the blood-brain barrier temporarily to improve drug delivery to tumors.

“With collaboration between the lab and clinic, alongside industry partners and even between hospitals, we can finally make strides I haven’t seen in my entire career,” Dr. Hwang said. “It’s an incredibly inspiring time for all of us.”

Why it matters

Experts from organizations as diverse as MaxCyte, ScaleReady, RoosterBio, PSC Biotech, Qiagen, FujiFilm and the Frederick County Office of Economic Development came together for the daylong conversation.

Michael Friedlander, Ph.D., executive director of the Fralin Biomedical Research Institute at Virginia Tech, emphasized the critical role of regional partnerships in fulfilling the potential of these emerging therapies. He pointed to the collaborative research between Children’s National and Virginia Tech on brain tumors, where bioengineers and cancer researchers are working side-by-side to create new treatments.

“We are now able to begin delivering these leading-edge therapies to patients,” Dr. Friedlander said. “For example, those who live in rural settings often have much less access to such frontline medical innovations. By collaborating with Children’s National and gaining access to urban pediatric populations, as well as patients in our more rural area, we can start to bring these therapies to a much broader audience.”

What’s next

Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, observed that other regions in the U.S. are uniting to advance scientific discoveries with the backing of government, academia and industry. He hopes to see similar collaboration across the D.C., Maryland, and Virginia area, known as the DMV. Children’s National is leading an initiative called CHARM – the Capital Health and Mid-Atlantic Regenerative Medicine – to bring regional experts together for webinars, networking events and partnership opportunities.

“There’s significant interest in cell and gene therapy worldwide,” said Dr. Hanley, a symposium host. “I see an even greater interest in creating cell and gene therapy hubs. The time is right for our mid-Atlantic region, and I’m excited to see what unfolds in the next five years.”

A clean room at CNRI.

CellBuilder: A ready-made solution for cell & gene therapy manufacturing

A clean room at CNRI.

With CellBuilder and our global partnerships, Children’s National hopes to expand access to groundbreaking cell and gene therapy treatments as they take off in the next five years.

With cell and gene therapies poised to reshape cancer and rare disease treatments, researchers at Children’s National Hospital are pioneering ready-to-use solutions that will bring these cutting-edge therapies directly to hospitals and other treatment centers, shrinking the distance between doctors and patients.

“The next five years are going to be a period of tremendous growth for cell and gene therapy,” said Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National. “Currently, there’s no shortage of interest from the medical community, but there’s a shortage of people who can manufacture and administer this care. We’re looking for ways to get these treatments to the patients by providing other institutions the tools they need to launch these programs cost-effectively, safely and efficiently.”

Called CellBuilder, the starter kits for cell and gene therapy programs could transform the landscape for pediatric patients.

The big picture

Dr. Hanley and many members of the Children’s National team have been working in cell and gene therapy for more than a decade, gaining extensive experience in the technical and regulatory hurdles inherent in creating treatments that target diseases at their source.

In cell therapy, a specific cell type is modified and transferred to a patient with a payload that can target a disease or disorder. For example, T cells may be modified and delivered to patients to teach their immune systems to fight cancer.  In gene therapy, a patient’s genetic code is modified to treat or prevent diseases, such as sickle cell disease, cancers and other genetic disorders. This can be done by introducing a healthy copy of a gene, repairing a faulty gene or altering a gene’s function.

Children’s National has become a leader in manufacturing virus-specific T cells, one method of delivering cell therapies, and the Cellular Therapy Program has conducted consortium-led, multi-center trials. Many other healthcare sites across the country want to start programs offering this care at their facilities.

The holdup in the field

Starting a cell and gene therapy program from scratch can take years of effort, training and money. That’s why Jay Tanna, M.S., R.A.C., quality assurance manager of the Cellular Therapy Program at Children’s National, said the team is creating CellBuilder starter kits, which include the manufacturing protocol and the resources necessary to launch a cell therapy program almost instantly.

“With a suitable knowledge base, institutions can start their own cellular therapy program at the point of care, using our manufacturing protocols, vetted reagents and other key elements of the process,” Tanna said. “Of course, interested institutions would have to meet regulatory requirements and establish a clean room to manufacture these therapies. If they want to use CellBuilder to run a clinical trial, they can do that. If they want to take it to become a licensed product, they can do that, too.”

Children’s National has worked with more than five institutions to build their virus-specific T-cell program and is now using the kits to accelerate and commercialize the process to increase patient access. The lab has also entered into a memorandum of understanding with the Tokyo-based Hitachi Global Life Solutions, Inc., an innovative modular clean room manufacturer, with the goal of offering a bundled solution.

Why we’re excited

Dr. Hanley and his colleagues say that the partnerships Children’s National is forging as they consult with other experts in this field will expand access to cell and gene therapy across the country—and hopefully around the world.

“It used to be that, to get a CAR T cell, you would collect the cells at Children’s National, ship them to a company like Novartis, have the therapy manufactured there and then shipped back,” said Michael Keller, M.D., who co-led a first-of-its kind immunotherapy trial as the Translational Research Laboratory director at the Children’s National Cell Enhancement and Technologies for Immunotherapy Program. “It was expensive, time-consuming and limited patient access. Now, there’s growing interest in manufacturing at each site, just like you would with a bone marrow transplant.”

With CellBuilder and our global partnerships, Children’s National hopes to expand access to groundbreaking cell and gene therapy treatments as they take off in the next five years, extending lifetimes and improving the quality of life for children suffering from rare disorders.

“We’re trying to capture the momentum underway in the field by providing this kit so that institutions don’t have to know how to do everything,” Dr. Hanley said. “We provide all the knowledge, a reagent list and everything else they need—and they provide the care.”

Leaders from pediatric healthcare, federal organizations, academia, industry and patient advocacy groups gathered at the Children’s National Research & Innovation Campus.

Access4Kids: A new model to pay for pediatric cell and gene therapies

Science is pioneering cures for pediatric rare diseases in a coming wave of new cell and gene therapies. However, the biopharmaceutical industry’s insistence on large patient populations and high profit margins may prevent these life-saving treatments from reaching the children who desperately need them. When successful therapeutics fail to see commercialization, experts say they have fallen into the “Valley of Death.”

To address this, leaders from pediatric healthcare, federal organizations, academia, industry and patient advocacy groups gathered at the Children’s National Research & Innovation Campus. Their objective: build a new framework to deliver these transformative drugs to clinics worldwide.

Meet the team forming Access4Kids, a nonprofit whose mission is to build new pathways to pay for cures and provide hope to children with life-limiting diseases. This group is working to change medicine and how we pay for it, under the leadership of Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research, Crystal Mackall, M.D., director of the Stanford Center for Cancer Cell Therapy, Julie Park, M.D., Oncology Department chair at St. Jude Children’s Research Hospital, and Alan Wayne, M.D., pediatrician-in-chief at Children’s Hospital Los Angeles.

Dr. Bollard and her laboratory

Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

Dr. Bollard and her laboratory

Cancer Grand Challenges NexTGen team members (left to right): Amy Hont, M.D., AeRang Kim, M.D., Nitin Agrawal, Ph.D., Catherine Bollard, M.D., M.B.Ch.B., Conrad Russell Cruz, M.D., Ph.D., Patrick Hanley, Ph.D., and Anqing Zhang.

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, has been selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children. Cancer Grand Challenges is a global funding platform, co-founded by Cancer Research UK and the National Cancer Institute in the U.S., that supports a community of diverse, global teams to come together, think differently and take on some of cancer’s toughest challenges.

The Cancer Grand Challenges NexTGen team, co-led by University College London’s Martin Pule, M.D., will be working to develop next-generation cell therapies for children with solid cancers. Cancer is a leading cause of death by disease in children worldwide. Although survival has increased for some pediatric cancers, such as blood cancers, survival for some solid tumors has seen little improvement for more than 30 years. The team hopes to build a much deeper understanding of childhood cancers and develop and optimize novel therapies for children with solid tumors, ultimately hoping to improve survival and diminish the lifelong toxicities often experienced by survivors.

“With our Cancer Grand Challenge, we hope to bring next-generation CAR T-cell therapies to children with solid tumors,” said Dr. Bollard. “What excites me most is the energized, passionate group of people we’ve brought together to take this challenge on. Big problems remain to be addressed, but we believe they can be solved, and that we’re the team to solve them.”

“NexTGen represents crucial and overdue work. It has hope written all over,” said Sara Wakeling, patient advocate on the team and CEO and co-founder of Alice’s Arc, a children’s charity for rhabdomyosarcoma. “NexTGen hopes to transform the way these aggressive solid tumors are treated with less toxic side-effects, giving the children a real chance at growing up and realizing their potential. I’m so proud to be part of this exceptional team of scientists, clinicians and advocates who want to change the story for those diagnosed.”

The NexTGen team unites scientists and clinicians with expertise in immunology, proteomics, mathematics and more, across eight institutions throughout the U.S., U.K. and France. The Children’s National investigators that will also join are:

  • Nitin Agrawal, Ph.D., associate professor in the Center for Cancer and Immunology Research at Children’s National.
  • Conrad Russell Cruz, M.D., Ph.D.,principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies at Children’s National.
  • Patrick Hanley, Ph.D., chief and director of the cellular therapy program at Children’s National and leader of the Good Manufacturing Practices laboratory.
  • Amy Hont, M.D., oncologist in the Center for Cancer and Immunology Research at Children’s National.
  • AeRang Kim, M.D., oncologist in The Center for Cancer and Blood Disorders at Children’s National.
  • Holly Meany, M.D., oncologist in The Center for Cancer and Blood Disorders at Children’s National.
  • Anqing Zhang, biostatistician in the Biostatistics and Study Methodology Department at Children’s National.

The team, co-funded by Cancer Research UK, the National Cancer Institute and The Mark Foundation for Cancer Research, aims to bring much needed new treatments to children with solid cancers.

The NexTGen team is one of four new teams announced today as part of Cancer Grand Challenges, representing a total investment of $100m to diverse, global teams to take on some of the toughest challenges in cancer research.

“Cancer is a global issue that needs to be met with global collaboration. This investment in team science encourages diverse thinking to problems that have long hindered research progress,” said David Scott, Ph.D., director of Cancer Grand Challenges, Cancer Research UK. “Cancer Grand Challenges provides the multidisciplinary teams the time, space and funding to foster innovation and a transformative approach. NexTGen is one of four newly funded teams joining a scientific community addressing unmet clinical needs across cancer research.”

Find out more

Cancer Grand Challenges supports a global community of diverse, world-class research teams with awards of £20m/$25m to come together, think differently and take on cancer’s toughest challenges. These are the obstacles that continue to impede progress and no one scientist, institution or country will be able to solve them alone. Cancer Grand Challenges teams are empowered to rise above the traditional boundaries of geography and discipline.

Founded by the two largest funders of cancer research in the world – Cancer Research UK and the National Cancer Institute* in the U.S. – Cancer Grand Challenges aims to make the progress against cancer we urgently need. Cancer Grand Challenges currently supports more than 700 researchers and advocates across 10 countries, representing 11 teams are supported to take on 10 of the toughest challenges in cancer research.

The Cancer Grand Challenges NexTGen team, announced June 16, 2022, is taking on the initiative’s Solid Tumours in Children challenge. It is led by Dr. Bollard (Children’s National) and Dr. Pule (University College London), along with 23 co-investigators and 7 patient advocates, and is spread across eight institutions across the U.S., U.K. and France: Cardiff University; Children’s Hospital of Philadelphia; Children’s National Hospital; INSERM; the Institute of Cancer Research; Stanford Medicine; Stanford University; University College London. The Cancer Grand Challenges NexTGen team is funded by Cancer Research UK, the National Cancer Institute in the U.S. and The Mark Foundation for Cancer Research.

*The National Cancer Institute is part of the National Institutes of Health.

 

Hodgkin lymphoma cells

T-cell therapy alone or combined with nivolumab is safe and persistent in attacking Hodgkin’s lymphoma cells

Hodgkin lymphoma cells

Hodgkin’s lymphoma is a type of cancer that attacks part of the immune system and expresses tumor-associated antigens (TAA) that are potential targets for cellular therapies.

It is safe for patients with relapsed or refractory Hodgkin’s lymphoma (HL) to receive a novel tumor-associated antigen specific T-cell therapy (TAA-T) either alone or combined with a checkpoint inhibitor, nivolumab — a medication used to treat several types of cancer. The study, published in Blood Advances, further suggests that nivolumab aids in T-cell persistence and expansion to ultimately enhance anti-tumor activity. This offers a potential option for patients who do not have a durable remission with checkpoint inhibitors alone or are at a high risk of relapse after a transplant.

“The fact that this combination therapy is so safe was very encouraging for the treatment of patients with lymphomas,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital. “In addition, this data allows us to consider this combination immunotherapy for other patients, including those with solid tumors.”

HL is a type of cancer that attacks part of the immune system and expresses tumor-associated antigens (TAA) that are potential targets for cellular therapies. While it may affect children and adults, it is most common in those who are between 20 and 40 years old. The survival rate for this condition has improved due to scientific advances.

A new approach in cancer therapy is the use of “checkpoint inhibitors,” which are a class of drugs that block some of the inhibitory pathways of the immune system to unleash a powerful tumor killing immune response. Similarly, T-cell therapies have also shown to enhance anti-tumor immune response. Therefore, combining these novel immune therapies is an attractive and targeted alternative to conventional untargeted therapies – such as chemotherapy and radiation – which not only kill the tumor cells but also can kill healthy cells and tissues.

“In five to 10 years we can get rid of chemotherapy and radiation therapy and have an immunotherapy focused treatment for this disease,” said Dr. Bollard.

To determine the safety of infusing TAA-T with and without checkpoint inhibitors, eight patients were infused with TAA-specific T-cell products manufactured from their own blood. Two other patients received TAA-T generated from matched healthy donors as adjuvant therapy after hematopoietic stem cell transplant. According to Dave et al., the TAA-T infusions were safe and patients who received TAA-T as adjuvant therapy after transplant remained in continued remission for over two years.

Of the eight patients with active disease, one patient had a complete response, and seven had stable disease at three months, three of whom remained with stable disease during the first year.

“Treating Hodgkin’s lymphoma with cellular therapy has not yet achieved the same success that we have seen for other lymphoma subtypes,” said Keri Toner, M.D., attending physician at Children’s National. “This study brings us closer to overcoming some of the current barriers by developing methods to improve the persistence and function of the tumor-specific T-cells.”

This study builds upon the researchers’ latest findings in another study, which demonstrated that TAA-T manufactured from patients were safe and associated with prolonged time to progression in solid tumors.

“The addition of a checkpoint inhibitor like Nivolumab to the TAA-T treatment is a powerful next step, but previously, the safety of this combination was unknown,” said Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, leader of the GMP laboratory and co-author of the study. “Now that we have demonstrated a safety profile, the next step will be to evaluate the efficacy of this combination in a larger subset of patients.”

inside a GMP lab

Cell therapy manufacturing process ramps up to meet increased demand for T-cell products

inside a GMP lab

The new laboratory space includes floor-to-ceiling windows and brand new, state-of-the-art GMP lab suites.

Since Children’s National Hospital began its pediatric cellular therapy program in 2013, it has received more than $5 million in annual funding, treated over 200 patients, manufactured more than 400 cell-based products and supported over 25 clinical trials.

One of the in-house programs supporting this work is the Good Manufacturing Practices (GMP) facility. Patrick Hanley, Ph.D., chief and director of the cellular therapy program at Children’s National and leader of the GMP laboratory, explained that the first patient received a dose of less than 10 million cells in May 2014. Fast forward to now, the lab uses liters of media, automated bioreactors and multiple staff, making upwards of 12 billion cells per run — a growing production scale that enables many different options. Using cells as an off-the-shelf technology is one of those.

The cell therapy program exports these off-the-shelf products beyond Children’s National to make them available for kids across the country. Catherine Bollard, M.D., MBChB., director of the Center for Cancer and Immunology Research at Children’s National, and Michael Keller, M.D., director of the Translational Research Laboratory in the Program for Cell Enhancement and Technologies for Immunotherapy (CETI) at Children’s National, each led clinical trials with hospitals across the United States, including the first-ever cellular therapy clinical trial run through the Children’s Oncology Group.

To meet the high demand for cell therapy trials at Children’s National, the GMP lab moved to a larger space, doubling the team’s capacity to produce alternative treatment options for patients and facilitate the lab’s ability to support clinical divisions throughout the hospital.

The GMP lab is exploring how to make cell products more consistent — regardless of patient-to-patient variability. They are also hoping to delineate the characteristics that ensure quality cell products, educate other facilities, enhance the overall knowledge of how to safely manufacture these products and make these technologies more available and affordable to the patients who need them.

Among Hanley’s many goals for the GMP lab, one is to improve the transition from when an investigator discovers a product in the translational research lab to when it is manufactured for patients.

“To improve this transition, we have started a process development team that will learn the process alongside the research team, replicate it, and then train the staff who manufacture the product for patients,” said Hanley. “In addition to providing a better training opportunity for the manufacturing staff, it allows us to work with the investigators earlier on to identify changes that will need to be made to translate the products to patients, ultimately resulting in safer, more potent immunotherapy products.”

While cell therapy has seen increased interest in the last 10 years, there are still some challenges in the field, given that it is not as mature as other scientific areas. The lack of trained staff, scalability of cell and gene therapy, the variability between patients and products, delayed FDA approvals and rejection of licensing applications for cell therapy products — are barriers that scientists and companies often face.

“Each of us has a unique immune system, and that means that if we try and make a product from it, it will not behave like any other, so the number of cells, the potency the alloreactivity — it is all different,” said Hanley. “T-cells are a living drug that expand in the body at different rates, are composed of different types of T-cells, and release different cytokines and in different amounts.”

This all ties back to the process development and basic research. The better researchers can characterize the products under development, the more they will know about how the products work and the easier it will be to tie these products to patient outcomes.

Meet some of the Children’s National multidisciplinary experts who join forces to lead the cell therapy space.

Jay Tanna, M.S., quality assurance manager, has extensive experience with drug development at Children’s National as well as Sloan Kettering, another premier cell therapy institution. He has a Masters in Pharmaceutical Manufacturing and a Regulatory Affairs Certification (RAC) in U.S. FDA drugs and biologics regulations from the Regulatory Affairs Professional Society (RAPS).

Kathryn Bushnell, M.T. (ASCP), the cell therapy lab manager, oversees Stem Cell Processing. She has 20 years of experience with hematopoietic progenitor cells and cellular therapy, starting her career as a medical technologist at MD Anderson Cancer Center.

Nan Zhang, Ph.D., assistant director of manufacturing at Children’s National, has worked at Wake Forest and the National Institutes of Health developing various cellular therapies. Zhang chaired the cell processing session at the annual meeting of the American Society of Hematology in 2020.

Abeer Shibli, M.T., is a specialist in the cellular therapy laboratory with extensive experience in the processing of cellular therapy products. She has over 10 years of experience as a medical technologist, is specialized in blood banking and transfusion medicine and is one of the senior technologists in the lab.

Chase McCann, M.S.P.H., Ph.D., is the cell therapy lab lead for manufacturing at Children’s National Hospital. He recently completed his Ph.D. training in Immunology and Microbial Pathogenesis at Weill Cornell Medicine in New York. Much of his graduate research focused on developing and enhancing cellular therapies for HIV while identifying common mechanisms of escape, shared by both HIV and various cancers, which limit the efficacy of current cell therapies. Previously, McCann worked as the laboratory coordinator for the HIV Prevention Trials Network, and now oversees the manufacturing of many cell therapies supporting the many clinical trials currently underway at Children’s National.

Anushree Datar, M.S., the cell therapy lab lead for immune testing and characterization, oversees the release testing of products manufactured in the GMP for safety and function before they can be infused in patients. She also leads a part of the research team investigating the improvement in immune function after cell infusion.

Dr. Bollard is also the director of the Program for Cell Enhancement and Technologies for Immunotherapy and president of the Foundation for the Accreditation for Cellular Therapy (FACT). Additionally, in 2019, she became a member of the Frederick National Laboratory Advisory Committee (FNLAC) for the NIH and an ad hoc member of the Pediatric Oncologic Drugs Advisory Committee (ODAC) for the FDA. She has been an associate editor for the journal Blood since 2014 and in 2020 was appointed editor-in-chief of Blood Advances (starting Fall 2021). Dr. Bollard has 21 years of cell therapy experience as a physician, sponsor and principal investigator.

Dr. Hanley serves as the commissioning editor of the peer-reviewed journal Cytotherapy, as the vice-president-elect (North America) of the International Society of Cell and Gene Therapy (ISCT), and board of directors member at FACT, which provides him visibility into various cell and gene therapies, manufacturing approaches, and other intangibles that make Children’s National facility one of the leaders in the field.

To find the full research program list and their experts, click here.

GMP group photo

Lab members celebrate the expansion of the GMP Laboratory.

Wilm's Tumor

PRAME-specific T cell product may facilitate rapid treatment in cancer settings

Wilms Tumor

PRAME is a cancer-testis antigen that plays a role in cancer cell proliferation and survival and is overexpressed in many human malignancies, including Wilms tumor. “Wilms Tumor (Nephroblastoma)” by euthman is licensed under CC BY 2.0.

Generated preferentially expressed antigen in melanoma (PRAME)-specific T cells from healthy donors can kill PRAME-expressing tumor cells in vitro, researchers at Children’s National Hospital found. Several novel epitopes, which are antigens that are recognized by the immune system, were also identified for enhanced matching, making this a potential therapeutic option for a broader patient group, according to a study published in Cytotherapy.

PRAME is a cancer-testis antigen that plays a role in cancer cell proliferation and survival and is overexpressed in many human malignancies, including melanoma, leukemia, sarcoma, renal cell cancer and Wilms tumor. PRAME also acts as a foreign substance in the body that can trigger the immune system by activating T cells, making it a good target for anticancer immunotherapy — especially for immunocompromised patients.

“The development of an effective off-the-shelf adoptive T-cell therapy for patients with relapsed or refractory cancers expressing PRAME antigen requires the identification of epitopes essential to the adaptive immune response, which are presented by major histocompatibility complex (MHC) class I and II, and are then recognized by the manufactured PRAME-specific T cell product,” said Amy Hont, M.D., oncologist for the Center for Cancer and Immunology Research at Children’s National Hospital. “We, therefore, set out to extend the repertoire of HLA-restricted PRAME peptide epitopes beyond the few already characterized and demonstrate the cytotoxic activity of PRAME-specific T cells to tumor cells known to express PRAME.”

Immunotherapy options for pediatric patients with high-risk malignancies, especially solid tumors, are few. Tumor-associated antigen-specific T cells (TAA-T) offer a therapeutic option for these patients, and Children’s National is building upon the success of the ongoing clinical trials to optimize this therapy and improve the treatment of our patients.

“These findings will also benefit patients because it better informs the pre-clinical studies of third party TAA-T to treat high-risk malignancies, so that we can move more quickly and safely to clinical trials,” said Dr. Hont.

Stanojevic et al. describes that the T-cell products killed partially HLA-matched tumors, and that this enhanced disintegration of tumor cells compared with non-specific T cells suggests an anti-tumor potential for a clinical trial evaluation to determine the safety and efficacy. Further research about the PRAME-specific T cells will help inform a treatment alternative for patients with solid tumors in the future.

The researchers generated a PRAME-specific T cell bank from healthy donor cells and demonstrated anti-tumor cytolytic activity against tumor lines partially HLA-matched to the T cells and known to express PRAME. By using epitope mapping, they identified several novel epitopes restricted to MHC class I or MHC class II to further inform HLA matching.

“Defining PRAME-specific T cells beyond HLA epitopes could be useful when developing T-cell therapies for worldwide application,” Stanojevic et al. write. “Moreover, creating off-the-shelf products has many potential advantages since such products are readily available for the treatment of patients with aggressive disease or patients for whom an autologous product cannot be manufactured.”

Additional authors from Children’s National are Maja Stanojevic, M.D., Ashley Geiger, M.S., Samuel O’Brien, Robert Ulrey, M.S., Melanie Grant, Ph.D., Anushree Datar, M.S., Ping-Hsien Lee, Ph.D., Haili Lang, M.D., Conrad R.Y. Cruz, M.D., Ph.D.,  Patrick J. Hanley, Ph.D., A. John Barrett, M.D, Michael D. Keller, M.D., and Catherine M. Bollard, M.D., M.B.Ch.B.

illustration of brain with stem cells

Innovative phase 1 trial to protect brains of infants with CHD during and after surgery

A novel phase 1 trial looking at how best to optimize brain development of babies with congenital heart disease (CHD) is currently underway at Children’s National Hospital.

Children with CHD sometimes demonstrate delay in the development of cognitive and motor skills. This can be a result of multiple factors including altered prenatal oxygen delivery, brain blood flow and genetic factors associated with surgery including exposure to cardiopulmonary bypass, also known as the heart lung machine.

This phase 1 trial is the first to deliver mesenchymal stromal cells from bone marrow manufactured in a lab (BM-MSC) into infants already undergoing cardiac surgery via cardiopulmonary bypass. The hypothesis is that by directly infusing the MSCs into the blood flow to the brain, more MSCs quickly and efficiently reach the subventricular zone and other areas of the brain that are prone to inflammation. The trial is open to eligible patients ages newborn to six months of age.


Learn more in this overview video.

The trial is part of a $2.5 million, three-year grant from the National Institutes of Health (NIH) led by Richard Jonas, M.D., Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D.. The project involves collaboration between the Prenatal Cardiology program of Children’s National Heart Institute, the Center for Cancer and Immunology Research, the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

“NIH supported studies in our laboratory have shown that MSC therapy may be extremely helpful in improving brain development in animal models after cardiac surgery,” says Dr. Ishibashi. “MSC infusion can help reduce inflammation including prolonged microglia activation that can occur during surgery that involves the heart lung machine.”

Staff from the Cellular Therapy Laboratory, led by director Patrick Hanley, Ph.D., manufactured the BM-MSC at the Center for Cancer and Immunology Research, led by Dr. Bollard.

The phase 1 safety study will set the stage for a phase 2 effectiveness trial of this highly innovative MSC treatment aimed at reducing brain damage, minimizing neurodevelopmental disabilities and improving the postoperative course in children with CHD. The resulting improvement in developmental outcome and lessened behavioral impairment will be of enormous benefit to individuals with CHD.

For more information about this new treatment, contact the clinical research team: Gil Wernovsky, M.D., Shriprasad Deshpande, M.D., Maria Fortiz.

t-cells attacking cancer cell

Children’s National spin-out cell therapy company receives funding

t-cells attacking cancer cell

Ongoing efforts by researchers at Children’s National Hospital to improve T-cell therapies have led to a spin-out company MANA Therapeutics which has announced a $35 million Series A financing. MANA is a clinical stage company creating nonengineered, allogeneic and off-the-shelf cell therapies that target multiple cancer antigens. Its EDIFY™ platform aims to educate T-cells that target multiple target multiple cell surface and intracellular tumor-associated antigens across a broad range of liquid and solid tumors, with an initial focus on relapsed acute myeloid leukemia (AML).

MANA was founded in 2017, and was based on the research and human proof-of-concept clinical trials conducted by Catherine Bollard, M.D., M.B.Ch.B., Conrad Russell Y. Cruz, M.D., Ph.D., Patrick Hanley, Ph.D. and other investigators at Children’s National along with their colleagues at Johns Hopkins Medical Center. The trials demonstrated safety and anti-tumor activity of MANA’s approach, and Children’s National provided an exclusive license to MANA to further develop this promising technology into commercial products in the field of immuno-oncology.

MANA Therapeutics recruited an experienced leadership team from industry including Martin B. Silverstein, M.D., president and CEO, who is a former senior executive at Gilead Sciences when they acquired Kite Pharma, one of the leading cell therapy companies, as well as Madhusudan V. Peshwa, Ph.D., chief technology officer, who joined from GE Health Care where he had been Chief Technology Officer and Global Head of R&D for Cell and Gene Therapies.

“MANA is building upon the strong foundational science established at Children’s National with a unique approach that promises to produce off-the-shelf allogeneic therapies that do not compromise on safety or efficacy,” said Marc Cohen, co-founder and executive chairman of MANA Therapeutics. “I look forward to continuing to support the MANA team as they advance their internal pipeline for the treatment of AML and select solid tumors, and expand the potential of EDIFY through strategic partnerships focused on new target antigens and cancer types.”

An international leader in the immunotherapy field, Dr. Bollard was an early believer in the potential of immune cell therapies to dramatically improve the treatment of patients with cancer and patients with life-threatening viral infections. Recently, she and her team at the Children’s National Center for Cancer and Immunology Research published findings in Blood showing T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function.

“Over the past decade we have seen tremendous progress in cancer research and treatment and are beginning to unlock the potential of cell therapy for a variety of tumor types,” said Dr. Bollard. “The human proof-of-concept trials conducted by my team and colleagues showed potential for a nonengineered approach to educating T-cells to attack multiple tumor antigens, which MANA is expanding even further through refinement of the manufacturing process for an allogeneic product and application to a broader set of antigens in a variety of clinical indications and settings.”