Sascha P Haubner, MD

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the field of cellular immunotherapy and yields long-term remissions in several hematological malignancies including B cell acute lymphoblastic leukemia (B-ALL), B cell non-Hodgkin lymphomas (B-NHL) and multiple myeloma. Even though CAR T cell therapy has in principle the potential to achieve similar outcomes in acute myeloid leukemia (AML), re-directing the approved CD19-specific CAR designs against myeloid target antigens has been associated with AML resistance and myeloablative toxicities. These efficacy and safety limitations owe in large part to the challenge of identifying suitable target antigens and designing adequate receptors for effective recognition and safe elimination of AML. CAR T cell therapy in AML requires novel approaches that better adapt to the specific target biology and the associated bone marrow microenvironment. Multi-antigen targeting, logic-gating and emerging cell engineering solutions offer new possibilities to better direct T cell specificity and sensitivity towards AML, and investigation of AML-intrinsic resistance and leukemic microenvironmental factors is poised to reveal additional targetable AML vulnerabilities.

Our laboratory leverages pre-clinical models and patient samples to understand mechanisms of AML resistance and toxicities in the context of CAR therapies including those under current clinical investigation, to rationally adapt novel CAR strategies to the complex AML biology and microenvironment.