Fall 2025 Grantee Highlight:
Saad Kenderian
Saad Kenderian, MD, PhD
Associate Professor of Medicine, Co-Leader, Cancer Immunology Immunotherapy, Mayo Clinic
Chimeric antigen receptor T cell (CAR T) therapy has transformed the treatment of certain blood cancers, offering new hope to patients with otherwise limited options. However, many patients do not experience lasting benefit, and the approach has shown limited success in solid tumors.
The Kenderian Laboratory investigates why these therapies lose durability over time, with a focus on understanding resistance and side effects in engineered immune cells. Their goal is to develop next-generation immunotherapies for cancer and autoimmune disease.
Recent work from the lab has identified cellular senescence—a permanent, dysfunctional aging state—as a key driver of CAR T cell failure. When T cells enter this state, they lose their ability to multiply and kill cancer cells effectively and instead secrete inflammatory signals that can further impair the immune response. The team has shown that activation of the gene MYC plays a central role in triggering this process in certain CAR T cell populations, diminishing their antitumor activity in both experimental models and patient samples.
This project aims to determine which MYC-driven pathways contribute to harmful senescence and which support effective CAR T cell function. By distinguishing these mechanisms, the team seeks to guide the design of improved CAR T treatments that remain effective for longer and benefit a broader range of patients.
