B7-H3: An Attractive Target for Antibody-based Immunotherapy.
B7-H3: An Attractive Target for Antibody-based Immunotherapy.
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DOI：
10.1158/1078-0432.ccr-20-2584
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发表时间：
2021-03-01
期刊：
影响因子：
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通讯作者：
Ferrone S
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文献类型：
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作者：
Kontos F;Michelakos T;Kurokawa T;Sadagopan A;Schwab JH;Ferrone CR;Ferrone S
The recent impressive clinical responses to antibody-based immunotherapy have prompted the identification of clinically relevant tumor antigens that can serve as targets in solid tumors. Among them, B7-H3, a member of the B7 ligand family, represents an attractive target for antibody-based immunotherapy: it is overexpressed on differentiated malignant cells and cancer initiating cells, with limited heterogeneity, and high frequency (60% of 25,000 tumor samples) in many different cancer types, but has a limited expression at low level in normal tissues. In non-malignant tissues, B7-H3 has a predominantly inhibitory role in adaptive immunity, suppressing T-cell activation and proliferation. In malignant tissues, B7-H3 inhibits tumor antigen-specific immune responses, leading to a pro-tumorigenic effect. B7-H3 also has non-immunological pro-tumorigenic functions, such as promoting migration and invasion, angiogenesis, chemoresistance and endothelial-to-mesenchymal transition as well as affecting tumor cell metabolism. As a result, B7-H3 expression in tumors is associated with poor prognosis. Although experimental B7-H3 silencing reduces cancer cell malignant potential, there has been limited emphasis on the development of B7-H3 blocking antibodies, most likely because the B7-H3 receptor remains unknown. Instead, many antibody-based strategies utilizing distinct effector mechanisms to target B7-H3-expressing cancer cells have been developed. These strategies have demonstrated potent anti-tumor activity and acceptable safety profiles in preclinical models. Ongoing clinical trials are assessing their safety and efficacy in patients. Identification of the B7-H3 receptor will improve our understanding of its role in tumor immunity, and will suggest rational strategies to develop blocking antibodies which may enhance the therapeutic efficacy of tumor immunity.
