(Clockwise from upper left) Dr. Tal Cohen, Dr. Doris Ponce, Dr. Sandeep Raj, Dr. Jonathan Peled, Dr. Yeon Joo Lee, Dr. Sergio Giralt, and Winston Chang had their research featured at the 2025 Tandem Meetings co-hosted by the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research.
Physicians and scientists from Memorial Sloan Kettering Cancer Center (MSK) presented advances in transplantation and cellular therapies at the Tandem Meetings, a joint event hosted by the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research from February 12 to 15, 2025, in Honolulu.
Three presentations at the meeting highlighted new ways to improve outcomes for people with blood cancers, including preventing a potentially life-threatening complication of allogeneic (donor-derived) stem cell transplantation and increasing the effectiveness of chimeric antigen receptor (CAR) T cell therapy.
Researchers Uncover Why the Lifecycles of CAR T Cell Therapies May Be Getting Cut Short
CAR T therapy is an effective treatment for many types of cancer. This approach involves engineering a patient’s immune cells in a laboratory to recognize cancer and then infusing them back into the body. However, this therapy isn’t effective for everyone, and researchers have been on a mission to figure out why. Recently, MSK investigators may have found a clue by studying how the body tags specific cells for destruction.
A research team in the lab of cellular therapist and early drug development specialist Christopher Klebanoff, MD, including lead post-doctorate researcher Fei Yi, MD, PhD, and pediatric instructor Tal Cohen, MD, hypothesized that CAR T cells may be tagging themselves for self-destruction before they have a chance to eliminate cancer. The team uncovered that two proteins, FAS and FAS-L, that are known to regulate the lifecycles of white blood cells also govern the lifespan of engineered CAR T cells used to treat people with cancer. The investigators found that disrupting the FAS signaling pathway in modified CAR T cells prolonged their lifespan. Additionally, they observed enhanced survival in leukemia and lymphoma mice models treated with the modified CAR T cells. Their findings suggest that inhibiting the expression of the FAS protein on CAR T cells could serve as a potent treatment strategy. Read the abstract.
This research was presented by Dr. Cohen, and it was awarded “Best Abstract” at this year’s meeting.
New Treatment Could Prevent a Life-Threatening Complication of Allogeneic Stem Cell Transplant in People With Blood Cancer
Bloodstream infections are a common and potentially life-threatening complication of allogeneic (donor-derived) stem cell transplantation, a treatment for blood cancer that involves taking blood or bone marrow stem cells from a healthy donor and giving them to another person. Infections after the stem cell transplant can be caused by disruption to the delicate balance of the gut microbiome, which weakens the connection between intestinal cells and allows harmful bacteria to enter the bloodstream. This complication often results in prolonged hospital stays and worse outcomes. Giving patients antibiotics before transplant can help prevent infection, but it also raises their risk of contracting an antibiotic-resistant bacterial infection, which can be fatal. Recently, a research team at MSK tested a new strategy to prevent infection by harnessing the power of a healthy microbiome.
Bone marrow transplant specialist Doris Ponce, MD, MS, presented the results of a phase 1b study that evaluated a new live biotherapeutic called SER-155 to prevent bloodstream infections in patients who receive stem cell transplants. The therapy is composed of 16 bacterial strains that provide a protective advantage against infectious pathogens. Thirty-four participants were enrolled in the clinical trial and were randomly assigned to receive either a placebo or SER-155 in combination with an oral antibiotic before undergoing a stem cell transplant. Results showed that patients did well on the treatment, and it was safe and effective. Bloodstream infections, duration of hospital stays, and overall antibiotic use were lower in the group that received SER-155 compared with the placebo group. Microbiome analysis post-transplant showed that the protective bacterial strains survived in patients’ gastrointestinal tracts to safeguard against infection. Read the abstract.
This research was awarded “Best Abstract” in the Infectious Disease Track at this year’s meeting.
Researchers Use Machine Learning Methods to Uncover Why Some With Large B Cell Lymphoma Don’t Respond to CAR T Cell Therapy
CAR T therapy is an effective treatment for some people with large B cell lymphoma, but it doesn’t work for everybody. Recently, researchers at MSK investigated why some people experience disease recurrence after this treatment.
Bone marrow transplant specialist Sandeep Raj, MD, presented the results of a study that used a machine learning model to predict how people with large B cell lymphoma would respond to CAR T cell therapy. Investigators analyzed data from 327 patients treated with CAR T cell therapy at MSK. They evaluated multiple data types, including PET-CT scans, blood markers for inflammation, immune cell quantities, and genomic sequences from tumor biopsies, to determine whether patients would respond favorably to treatment. The investigators found that using a machine learning model to evaluate multiple types of data improved the accuracy of predictions, suggesting that CAR T cell therapy outcomes depend on complex interactions between the immune system, tumor, and CAR T cells. These findings demonstrate the potential of machine learning to provide meaningful insights to inform clinical decision-making. MSK bone marrow transplant specialist and cellular therapist Roni Shouval, MD, PhD, was the study’s senior author. Read the abstract.
Noteworthy Presentations and Awards
Several other investigators from MSK presented research on a range of topics in immunotherapy and stem cell transplantation. Among them:
- Graduate student Winston Chang, a member of the Alan Hanash Lab, gave a presentation about the role of Paneth cells in intestinal epithelium recovery from transplant conditioning and graft-versus-host disease. Read the abstract.
- Bone marrow transplant specialist and cellular therapist Sergio Giralt, MD, gave the honorary Mortimer M. Bortin Lecture to commemorate the Founding Scientific Director of the International Bone Marrow Transplant Registry, now the CIBMTR. Dr. Giralt gave an overview of the rapid advances that have changed transplant practice in the past three decades.
- Infectious diseases specialist Yeon Joo Lee, MD, MPH, gave a presentation about fungal metagenomic next-generation sequencing in transplant infectious disease. Watch the session.
- Bone marrow transplant specialist and cellular therapist Jonathan Peled, MD, PhD, participated in a discussion about strategies to optimize the microbiome to improve outcomes for people who receive CAR T cell therapy. Watch the session.
