B7-H3 as a promising target for cytotoxicity T cell in human cancer therapy

Abstract

Targeting B7-H3 over-expressed tumor cells with anti-B7-H3 monoclonal antibodies inhibits tumor growth. Here we demonstrated the expression of B7 family homologue 3 (B7-H3) in a wide range of human tumor cells and further investigated whether B7-H3 could be served as a target for T-cell mediated immunotherapy against human cancers. The specific cytotoxic activity of activated T cell (ATC) armed with a novel anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) against tumor cell was evaluated in vitro and in vivo. In contrast with unarmed ATC, an increase in cytotoxic activity of B7-H3Bi-armed ATC against tumor cells was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, B7-H3Bi-armed ATC secreted more IFN-γ, TNF-α and IL-2 than unarmed ATC. Infusion of B7-H3Bi-armed ATC inhibited tumor growth in severe combined immunodeficiency (SCID) xenograft models, along with a significant survival benefit. Therefore, treatment with novel B7-H3Bi-armed ATC will be a promising strategy for current cancer immunotherapy.

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

“…Compared to unarmed ATC, enhanced cytotoxic activity and cytokine secretion of B7-H3Bi-armed ATC were observed. Infusion of B7-H3Bi-armed ATC also inhibited tumor growth in vivo, and significantly improved survival [51]. Researchers explored the antitumor ability of the antibody-drug conjugates (ADCs) that specifically destroyed B7-H3 positive expressing tumors, and found that established tumors and metastases were eradicated, and overall survival improved significantly, which demonstrate the anti-CD276-drug conjugates as promising reagents for highly selective broad-acting anti-cancer therapies [52].…”

New checkpoints in cancer immunotherapy

“…However, it is not evaluated in clinical trials. In 2016, one novel anti‐CD3 x anti‐B7‐H3 bispecific antibody (B7‐H3Bi‐Ab) was reported by Ma et al . They tested the specific cytotoxic activity of activated T cell (ATC) armed with this bispecific antibody against tumor cell in vitro and in vivo.…”

Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies

“…Although clinical responses to the standard anti-B7-H3 IgG alone have not been encouraging, its combination with other ICI or even with conventional therapies could offer opportunities. Novel engineered forms such as B7-H3 × CD3 bispecific antibodies may be valuable alternatives [80]. When the receptor(s) and signaling pathways of B7-H3 become better defined, more effective anti-B7-H3 inhibitors could potentially be explored.…”