Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.

High pre-existing alloreactive CD8+ T cells cause rapid rejection of allogeneic CAR T cells in lymphoma patients, affecting expansion and clinical outcomes.

• Why it matters: Understanding immune rejection mechanisms is crucial to improve the efficacy of allogeneic CAR T therapies, which face challenges unlike autologous treatments.
• What they did: The study analyzed 11 patients treated with a single lot of cema-cel using TCR sequencing, single-cell profiling, and lymphocyte assays, revealing immune and cellular factors influencing CAR T cell expansion.
• The result: Findings show that recipient alloreactive CD8+ T cells hinder CAR T expansion, while effector-like CAR T cells expand robustly, guiding strategies for donor selection and product design to enhance therapy success.