B7-H4 as a Target for Breast Cancer Immunotherapy

B7-H4 is a recently discovered B7-family molecule that has been shown to inhibit T cell proliferation and secretion of IL-2. Therefore, it has been classified as an immunosuppressive protein. Protein expression has been limited to subsets of activated T cells and is inducible in dendritic cells and macrophages. In contrast, protein expression is abundant on tissues from several malignancies, most notably breast adenocarcinoma. We proposed to generate antagonistic humanized anti-B7- H4 antibodies for the reversal of immune escape generated in breast cancer. Here we report the generation of 64 mouse monoclonal antibodies for the detection of B7-H4 by ELISA, and 25 for the detection of cell surface B7-H4 by flow cytometry. We are currently assessing the 25 antibodies suitable for flow cytometry for direct cytotoxic effect on human breast cancer cell lines as well as for antagonistic effects on B7-H4 function. Candidate antibodies will be subsequently humanized using genetic engineering techniques. Here, we also report several novel findings not yet reported in published literature and not anticipated in our grant proposal.