Antibody Gene Diversity Libraries and Phage Display to Generate Recombinant Human Antibodies for Prostate Cancer Therapy

Principal Investigators - James D. Marks MD, PhD | Jeffry Simko, MD

The aim of this project is to identify novel antibodies that can specifically target prostate cancer cells, and to develop these antibodies for diagnostic and therapeutic applications.

From a vast library of human antibodies, we have identified more than 70 which bind specifically to prostate cancer cells in vitro, including those from hormone-refractory cell lines. The binding patterns of these antibodies are different from those of known anti-prostate cancer antibodies, suggesting that they bind to cell surface molecules which have not been previously targeted. Moreover, these antibodies specifically identify prostate cancer cells in immunohisto-chemical studies of patient tumor specimens, providing further evidence for their potential clinical relevance.

Some of these antibodies may exert a direct anti-neoplastic effect, either by disrupting the tumor cell's internal signaling pathways, or by stimulating the immune system. Antibodies can also be conjugated to radioactive particles or to liposomes containing chemotherapeutic agents.

We have focused on antibodies which are rapidly taken up into the cell interior once they bind to the cell surface. They thus can be used as a "payload delivery" system for radiation therapy or chemotherapy concentrated only at the site of the tumor, allowing higher doses to the tumor and minimizing the side effects of systemic therapy. In the coming year we will continue to develop this repertoire of antibodies, test them for consistency of immunohistochemical staining of patient tissue specimens, identify the tumor-specific molecules which they target, and begin to test their efficacy in vivo in mouse models.