TY - JOUR TI - Selective recruitment of γδ T cells by a bispecific antibody for the treatment of acute myeloid leukemia AU - Ganesan, Rajkumar AU - Chennupati, Vijaykumar AU - Ramachandran, Balaji AU - Hansen, Michael Riis AU - Singh, Sanjaya AU - Grewal, Iqbal S. T2 - Leukemia AB - Despite significant progress over the last few decades in the treatment of acute myeloid leukemia (AML), there still remains a major unmet medical need for this disease. Immunotherapy approaches for redirecting pan CD3+ T cells to target leukemia blasts have shown limited efficacy in clinical trials and often accompanied with severe toxicity in AML patients. We designed an alternative engager molecule (Anti-TRGV9/anti-CD123), a bispecific antibody that can simultaneously bind to the Vγ9 chain of the Vγ9Vδ2+ γδ T cell receptor and to AML target antigen, CD123, to selectively recruit Vγ9+ γδ T cells rather than pan T cells to target AML blasts. Our results suggest that prototypic bispecific antibodies (a) selectively activate Vγ9+ γδ T cells as judged by CD69 and CD25 surface expression, and intracellular Granzyme B expression, (b) selectively recruit Vγ9+ γδ T cells into cell–cell conjugate formation of γδ T cells with tumor cells indicating selective and effective engagement of effector and target tumor cells, and (c) mediate γδ T cell cytotoxicity (in vitro and in vivo) against tumor antigen-expressing cells. Collectively, these findings suggest that selectively redirecting Vγ9+ γδ T cells to target AML blasts has a potential for immunotherapy for AML patients and favors further exploration of this concept. DA - 2021/02/01/ PY - 2021 DO - 10.1038/s41375-021-01122-7 DP - www.nature.com SP - 1 EP - 11 LA - en SN - 1476-5551 UR - https://www.nature.com/articles/s41375-021-01122-7 Y2 - 2021/02/04/03:28:19 ER -