Developing a 7033 CAR-T cell pathway to overcome AML heterogeneity
Silva H, Martin G, Birocchi F, et al. CD70 CAR T Cells Secreting an Anti-CD33/Anti-CD3 Dual Targeting Antibody Overcome Antigen Heterogeneity in AML. Blood. 2024; (doi: 10.1182/blood.2023023210).
Scientists believe they have identified a way to circumvent the antigen heterogeneity that has challenged chimeric antigen receptor (CAR) T cell treatment in the setting of acute myeloid leukemia (AML). A CAR construct targeting CD70 has shown robust potential, but antigen escape reduces its impact. In response, researchers redesigned the CAR platform to target two antigens: CD70 and CD33. By engineering the CD70-targeted CAR T-cells to secrete a bispecific T cell engaging antibody molecule (TEAM) aimed at CD33, specific cytoxicity was achieved across all AML cell lines. In T cells isolated from AML patients, CD33 TEAMs were able to redirect them to activate, secrete cytokines, and eradicate tumor targets despite exposure to prior cytotoxic therapies and, importantly, without any additional increase in tissue toxicity. The findings, suggesting that this approach eradicates CD33- or CD70-deficient AML, justify further investigation, according to the study authors.