Human cancer immunotherapy strategies targeting B7-H3 A, blockade of B7-H3 with blocking mAbs neutralizes inhibitory signaling in its unidentified receptor(s)

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Human cancer immunotherapy strategies targeting B7-H3 A, blockade of B7-H3 with blocking mAbs neutralizes inhibitory signaling in its unidentified receptor(s) in T cells, NK cells, and other immune cells enabling effector function. Human cancer immunotherapy strategies targeting B7-H3 A, blockade of B7-H3 with blocking mAbs neutralizes inhibitory signaling in its unidentified receptor(s) in T cells, NK cells, and other immune cells enabling effector function. B, B7-H3–specific ADCC initiated by Fc receptor engagement of NK cells and other immune cells induces death of tumor cells. ADCs bind to B7-H3 expressed by tumor cells and are internalized and generate cytotoxicity to tumor cells. C, CD3/B7-H3–bispecific antibodies bind to tumor-expressed B7-H3 and crosslink the CD3 portion of the TCR complex, activating T cells in the tumor microenvironment for tumor cell death. D, small-molecule inhibitors may bind to specific regions of B7-H3, such as the FG loop of the IgV domain, inhibiting the ligand–receptor interaction between tumor cells and immune cells, thus blocking receptor signaling and restoring effector function of immune cells. E, engineered CAR T cells recognize membrane B7-H3 and directly kill tumor cells. F, blocking mAbs against B7-H3 in combination with radiation, chemotherapy, targeted therapy, or other immune checkpoint inhibitors synergize to generate more effective antitumor immune responses. Elodie Picarda et al. Clin Cancer Res 2016;22:3425-3431 ©2016 by American Association for Cancer Research