Targeting U5 snRNP200 as a Selective Antigen for CAR-T Therapy in AML
Fujino T, Lewis J, Chen B, et al. Development of CAR T Cells Targeting a Surface RNA Binding Protein for the Treatment of Acute Leukemias. Cancer Discovery. 2026; (doi: 10.1158/2159-8290.CD-25-0920).
Scientists have developed a construct that they say overcomes challenges specific to using chimeric antigen receptor (CAR)-T cells to treat individuals with acute myeloid leukemia (AML). Success in this patient population has been limited by the absence of known AML-associated antigens that do not compromise normal hematopoietic precursor cells. As a workaround, the team designed CAR-T cells to target U5 snRNP200 — a donor autoantibody implicated in graft-versus-leukemia effect that is found in AML patients following successful allogeneic transplant. While U5 snRNP200 is expressed on the AML cell surface, it is not present on normal hematopoietic precursors, making it an ideal antigen for CAR-T therapy. Human and syngeneic models of AML illustrated the efficacy of anti-U5 snRNP200 CAR-T cells armored with IL-18, which demonstrated antigen gain on AML, prolonged remission, and protection against AML rechallenge.