Preclinical study of CD84 as specific target for acute myeloid leukemia CAR-T cell therapy

CAR-T cell therapy has transformed that treatment of hematologic malignancies, yet its application to acute myeloid leukemia (AML) remains challenging due to the scarcity of disease-specific antigens. The identification of a highly selective target is crucial to enhance efficacy while minimizing off-tumor toxicity. A preclinical study at the University of Padova (Italy) identified CD84 as a promising target for AML immunotherapy. It is robustly and stably expressed by blasts, particularly in relapsed disease, and negligible on normal hematopoietic stem/progenitor cells. The authors generated CD84-directed CAR-T cells and tested them in vitro and in vivo on clinically relevant models. The engineered cells exhibit potent cytotoxity against CD84-expressing AML cell lines and patient-derived xenograft (PDX) cells, eliminating leukemic blasts even with low CD84 expression. In AML PDX models, CAR-T treatment leads to sustained reduction of leukemia burden, doubling the survival of the treated animals compared to controls. No downregulation of CD84 expression on the blasts in the treated models is observed. CD84 CAR-T cells spare normal hematopoietic stem/progenitor cells that after treatment retain their repopulation potential in humanized models. The authors conclude that these findings establish CD84 as a target for AML immunotherapy.