
Tandem 2026: Roswell Park CAR T-Cell Pioneer Marco Davila, MD, PhD, Reports Discoveries on Treatment Resistance
Key Takeaways
- Preclinical data implicate macrophage activation by CAR T–secreted IFN-γ driving iNOS expression, dampening CAR cytotoxicity and contributing to ICAHT, CRS biology, and cytopenias.
- IFN-γ blockade prevented cytopenias and maintained antitumor efficacy, supporting myeloid-targeted strategies to reduce toxicity without compromising CAR T activity.
Roswell Park Comprehensive Cancer Center highlighted key presentations from its researchers at TCT 2026.
Experts from Roswell Park Comprehensive Cancer Center have been invited to share their recent discoveries at the
Invited talk by CAR T-Cell pioneer Dr. Marco Davila reveals strategy for overcoming resistance
A preclinical study led by senior author
Investigators focused on how macrophages – white blood cells capable of surrounding and “eating” cancer cells – can play a role in suppressing CAR T cells’ cancer-killing function and increasing toxicity. They discovered that interferon gamma (IFN-γ), a signaling protein called a cytokine that is produced by CAR T cells, causes the macrophages to express inducible nitric oxide synthase (iNOS), which in turn suppresses the CAR T cells’ cancer-killing function.
The macrophages can also contribute to the secretion of IFN-γ, causing immature T cells to transform into TH17 cells – which promote cytokine release syndrome – rather than Th1 cells, which increase the immune system’s anti-tumor response. However, high levels of IFN-γ contributed to cytopenias, a risk factor for infections, the number one cause for non-relapse mortality in patients. By blocking IFN-γ, the team was able to prevent cytopenias while preserving their anti-tumor efficacy.
“This is part of our larger body of work that advances strategies to overcome immunosuppressive barriers and improve T-cell therapies for hematologic cancers,” says Dr. Davila. He will give his invited presentation,
Oral abstracts
Liso-cel vs. axi-cel for B-cell lymphoma
While the two FDA-approved
Lisocabtagene maraleucel (liso-cel, brand name Breyanz) and axicabtagene ciloleucel (axi-cel, brand name Yescarta) target the CD19 protein expressed on the surface of B cells, helping a patient’s reengineered T cells locate and destroy B-cell lymphoma cells. But liso-cel is less likely than axi-cel to trigger such serious side effects as neurological toxicity and cytokine release syndrome (CRS), an inflammatory response caused by the immune system’s overreaction to the treatment.
Unlike controlled clinical trials, Real-World Studies involve data drawn from clinical practice in the real world, including electronic health records, insurance claims and cancer registries.
Lead author Nathan Denlinger of The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute will deliver the study results in
Patient Age, Race and Ethnicity Critical to Identifying Best Stem Cell Donor
Post-transplant use of the chemotherapy cyclophosphamide has dramatically reduced the risk of graft-versus-host disease (GVHD), a serious and potentially fatal complication in patients who receive allogeneic hematopoietic cell transplants, giving minority patients a wider choice of potential donors. But a study to be presented by first author
The research team analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) for 6,130 adult patients who received cyclophosphamide after undergoing an allogeneic transplant between 2013-2021. They found that Hispanic and non-Hispanic Black patients experienced higher overall survival with mismatched related and unrelated donors compared to matched unrelated donors, especially if the donor was over age 30. In contrast, white patients had the highest overall survival with matched unrelated donors.
“This study demonstrates that there’s no one-size-fits-all model to guide donor selection for allogeneic transplants,” explains Dr. Herr. “The patient’s race, ethnicity and age should be a strong consideration in identifying their stem cell donor. We have to continue applying insights from big data to identify patterns in which patients have the best outcomes following different types of transplant.”
Dr. Holtan featured on transplant panel
Dr. Hahn serves on CIBMTR Advisory Committee
Additional research highlights
The latest findings of several Roswell Park investigators will be highlighted during a poster session Thursday, Feb. 5, 6:30-8 p.m. MST in Hall AB. They include:
Ehsan Malek, MD , is first/presenting author andHan Yu, PhD, MBBS , is senior author onposter abstract 201 , “Induction Therapy Accelerates Immune Aging in Multiple Myeloma: Implications for Cellular Therapy Readiness.”Rahul Thakur, MD , is first/presenting author, withEhsan Malek, MD , senior author, ofposter abstract 242 , “Liquid MRD Detection Using Circulating Myeloma Cells Accurately Reflects Bone Marrow Disease Status Post-CAR T and ASCT.”Ajinkya Buradkar, MD , is first/presenting author, with senior authorFrancisco Hernandez-Ilizaliturri, MD , ofposter abstract 266 , “Real-World Incidence of CRS and ICANS across Commercial CAR T Products in B-Cell Malignancies and Multiple Myeloma: A Single-Center Analysis.”Ehsan Malek, MD , is first/presenting author ofposter abstract 400 , “Addressing Racial Disparities in Cellular Therapy Through Race-Agnostic Predictive Modeling in Multiple Myeloma.”- Trish Boersch is first/presenting author, with senior author
Erin Hughes, BSN, RN , ofposter abstract 728 , “Control the Documents! Revamping a TCT Program’s Standard Operating Procedures and Guidelines While Adhering to the Quality Management Plan.” Ehsan Malek is first and presenting author ofposter abstract 810 , “Improving Data Fidelity for CIBMTR Integration: The Impact of Unstructured M-Protein Reporting in Multiple Myeloma.”
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