Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy

Clin Cancer Res. 2016 Jul 15;22(14):3425-3431. doi: 10.1158/1078-0432.CCR-15-2428. Epub 2016 May 20.

Abstract

B7-H3 (CD276) is an important immune checkpoint member of the B7 and CD28 families. Induced on antigen-presenting cells, B7-H3 plays an important role in the inhibition of T-cell function. Importantly, B7-H3 is highly overexpressed on a wide range of human solid cancers and often correlates with both negative prognosis and poor clinical outcome in patients. Challenges remain to identify the receptor(s) of B7-H3 and thus better elucidate the role of the B7-H3 pathway in immune responses and tumor evasion. With a preferential expression on tumor cells, B7-H3 is an attractive target for cancer immunotherapy. Based on the clinical success of inhibitory immune checkpoint blockade (CTLA-4, PD-1, and PD-L1), mAbs against B7-H3 appear to be a promising therapeutic strategy worthy of development. An unconventional mAb against B7-H3 with antibody-dependent cell-mediated cytotoxicity is currently being evaluated in a phase I clinical trial and has shown encouraging preliminary results. Additional therapeutic approaches in targeting B7-H3, such as blocking mAbs, bispecific mAbs, chimeric antigen receptor T cells, small-molecule inhibitors, and combination therapies, should be evaluated, as these technologies have already shown positive results in various cancer settings. A better understanding of the B7-H3 pathway in humans will surely help to further optimize associated cancer immunotherapies. Clin Cancer Res; 22(14); 3425-31. ©2016 AACR.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • B7 Antigens / immunology*
  • Clinical Trials, Phase I as Topic
  • Humans
  • Immunotherapy / methods
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal
  • B7 Antigens
  • CD276 protein, human