Targeting immunotherapy for bladder cancer using anti-CD3× B7-H3 bispecific antibody

Abstract

Objective: B7-H3 is attractive for cancer immunotherapy with B7-H3 overexpressed tumors. To explore whether B7-H3 is an effective target for patients with bladder cancer, anti-CD3× anti-B7-H3 bispecific antibodies (B7-H3Bi-Ab) was armed with activated T cells (ATC) to kill bladder cancer cells. Methods: High expressions of B7-H3 on human bladder cancer cells were detected, including Pumc-91 and T24 cells, and their chemotherapeutic drug-resistant counterparts. ATC generated from healthy donors were stimulated with anti-CD3 monoclonal antibody and interleukin-2 (IL-2) for 13 days. The ability of ATC armed with B7-H3Bi-Ab to kill bladder cancer cells was detected by flow cytometry, LDH, Elisa, and luciferase quantitative assay. Moreover, ATC generated from bladder cancer patients was armed with B7-H3Bi-Ab to verity the cell killing by the methods as previously described. Results: Compared with unarmed ATC, a significant increased cytotoxicity of B7-H3Bi-Ab-armed ATC against bladder cancer cells was discovered. The B7-H3Bi-Ab-armed ATC secreted more IFN-γ, TNF-α, and expressed high levels of activation marker CD69. Interestingly, despite the presence of immunosuppression in patients and resistance in chemotherapeutic drug-resistant cancer cell lines, B7-H3Bi-Ab-armed ATC from patients with bladder cancer still showed significant cytotoxic activity against bladder cancer cells and their chemotherapeutic drug-resistant counterparts. Conclusion: B7-H3 is an effective target for bladder cancer. B7-H3Bi-Ab enhances the ability of ATC to kill bladder cancer cells. B7-H3Bi-Ab-armed ATC is promisingly to provide a novel strategy for current bladder cancer therapy.