Development of CAR T-cell therapies for T-cell lymphoma has been hampered by a limited range of targetable antigens. Shared expression of most T-lineage antigens between malignant and normal T cells promotes fratricide of CAR T cells and increases the risk of T-cell aplasia. We developed a CAR targeting CD5, a pan-T cell antigen commonly expressed in T-cell lymphoma. CD5 CAR T cells evade fratricide by rapidly downregulating CD5 protein expression and retain high cytotoxicity against T-cell lymphoma. An ongoing phase I clinical trial demonstrates curative potential of autologous CD5 CAR T cells in patients with peripheral T-cell lymphoma. CD5 CAR T-cell infusions were well tolerated and did not produce prolonged ablation of endogenous T cells. Other CAR T cell-based approaches for T-cell lymphoma will also be discussed.
Citation Format: Maksim Mamonkin. CAR T cells for T-cell lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA17.