B7-H4 as a Target for Breast Cancer Immunotherapy
Abstract
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 84 mouse monoclonal antibodies for the detection of B7-H4 by ELISA, 25 for the detection of cell surface B7-H4 by flow cytometry, and 5 suitable for immunohistochemistry of paraffin embedded tissue. Five antibodies have been subcloned and purified. While the antibodies have no direct cytotoxic effect, 2 of the clones block B7-H4 binding to T-cells. 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2013
- Accession Number
- ADA601838
Entities
People
- Alan L. Epstein
- Julie K. Jang
- Peisheng Hu
Organizations
- University of Southern California