T cell cytotoxicity toward hematologic malignancy via B7-H3 targeting.

Abstract

T cells are important effectors in anti-tumor immunity, and aberrant expression of B7 family members may contribute to tumor evasion. In this study, we analyzed expression of costimulatory molecules on human hematologic tumor cells and explored whether B7-H3, a member of the B7 superfamily, is an effective target for T cell mediated cytotoxicity toward hematologic malignancy. We investigated the bispecific antibody anti-CD3 × anti-B7-H3 (B7-H3Bi-Ab) for its ability to redirect T cells to target B7-H3 positive hematologic tumors, including Thp-1, K562, Daudi cells and a primary culture. The capacity of T cells armed with B7-H3Bi-Ab to kill hematologic tumors was evaluated by lactate dehydrogenase assay, flow cytometry, ELISA, and luciferase quantitative assay at an effector/target ratio of 5:1. Compared with unarmed T cells, B7-H3Bi-Ab-armed T cells exhibited significant cytotoxicity toward hematological tumor cells. Moreover, B7-H3Bi-Ab-armed T cells secreted more IFN-γ, TNF-α, IL-2, and Granzyme B and expressed higher levels of activating marker CD69 compared to unarmed T cells. In conclusion, B7-H3Bi-Ab enhances the ability of T cells to kill hematologic tumor cells, and B7-H3 may serve as a novel target for immunotherapy against hematologic malignancy.