Chimeric antigen receptor T cells get passed by leukemia

New immunotherapy treatments have led to dramatic responses in patients with chemotherapy-refractory solid tumors, leukemias, and lymphomas. One of these immunotherapies involves the adoptive transfer of autologous T cells gene-engineered to express a chimeric antigen receptor (CAR) that is a hybrid of an antibody and a T cell receptor (TCR) (1). The antibody portion provides new antigen specificity and after binding, the intracellular TCR domains of the CAR induce T cell activation and tumor killing. CAR T cells targeted against CD19, a protein expressed on nearly all normal and cancerous B cells, has mediated impressive responses in patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). Four groups have reported complete remission (CR) rates up to 90% in pediatric and/or adult patients with B-ALL, while the expected CR rate with chemotherapy alone is <30% (2-5). The number of patients treated with anti-CD19 CAR T cells has increased to beyond 100 and novel forms of relapse that allow tumor cells to avoid killing by CAR T cells have been identified. Although anti-CD19 CAR T cell therapy remains at an early stage of development, an understanding of the mechanisms of treatment escape may identify patients at high-risk for relapse and uncover new avenues to circumvent these relapses.