autologous anti-TIM-3/anti-CD123 CAR T cells

A preparation of autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD123 (interleukin-3 receptor alpha chain; IL3RA) and the inhibitory T-cell receptor T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3; TIM3; hepatitis A virus cellular receptor 2; HAVCR2), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-TIM-3/anti-CD123 CAR T cells target and bind to both CD123 and TIM-3 that are both expressed on the surface of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). This induces selective toxicity in CD123- and TIM-3-expressing LSCs. CD123, the alpha subunit of the IL-3 receptor, regulates the proliferation, survival and differentiation of hematopoietic cells. TIM-3, a transmembrane protein and immune checkpoint receptor, is associated with tumor-mediated immune suppression. TIM-3 has a higher specificity for LSC than CD123, whose expression is not limited to cancer cells. TIM-3 is not expressed on normal hematopoietic stem progenitor cells (HSCP), granulocytes, and macrophages. Targeting both TIM-3 and CD123 may reduce the on-target off-tumor effect and improve efficacy.