Preclinical development of anti B7-H4 therapeutic antibodies
Presentation Start/End Time:
Abstract Number: 4986
Author Block:
Jonathan A. Terrett, Lisheng Lu, Vidusha Devasthali, David King, Mary Huber, Chetana Rao-Naik, Sanjeev Gangwar, Vincent Guerlavais, Allen Zhang, Bilal Sufi, Liang Chen, Pina Cardarelli, James Phillips, Bing Chen, Haichun Huang, Dapeng Yao, Marco Coccia. Medarex, Inc., Milpitas, CA, Medarex, Milpitas, CA, Medarex, Sunnyvale, CA
B7-H4 ( O8E ) is a plasma membrane protein and a member of the B7 family of immune system co-stimulatory molecules. Its role and expression in the immune system remains to be fully characterized. However, B7-H4 has been shown to be absent from most normal tissues and highly expressed in multiple malignancies including breast cancer and ovarian cancer. Thus, even though this class of molecules may seem attractive as anti-cancer targets through immune stimulation, B7-H4 may be more tractable as a direct target on cancer cells. Here, we confirm the expression of B7-H4 in breast and ovarian cancer, as well as the limited normal tissue expression. In order to exploit the cancer specific expression of B7-H4 in a therapeutic setting we have developed fully human antibodies targeting B7-H4. These antibodies have high affinity and specificity and show both internalizing and ADCC activity on B7-H4 expressing cell lines. In a therapeutic xenograft model, an anti B7-H4 antibody-drug-conjugate is able to induce long term cures from a single low dose. Furthermore, this anti B7-H4 antibody is cross reactive with the mouse version of the protein, and shows no obvious on target toxicity despite the mouse protein showing similar normal tissue expression to humans. Thus B7-H4 is an attractive target for the development of targeted cytolytic antibodies for multiple cancer types. |
