Mechanisms and Refinements of PSCA Directed Antibody Therapy
Abstract
Prostate stem cell antigen is a cell surface protein expressed by a majority of localized, and metastatic prostate cancers. Our laboratory previously showed that a monoclonal antibody against PSCA, mAb 1GB, could inhibit the growth and metastasis of prostate cancers in immunodeficiency mice. The overall goal of this study was to determine the mechanism of action of this antibody, primarily whether it inhibited growth by recruiting the immune system or by direct crosslinking and signaling via the antigen on the cell surface. In addition, we proposed to test rational combination therapies to determine if we could improve upon the activity of the antibody itself. The major results reported here are that (1) the antibody 1GB inhibits tumor growth predominantly through an Fc independent mechanism of action, and (2) that combination therapies are context dependent. In some instances, castration synergized with antibody to prevent androgen independent tumor progression, while in others antibody promoted androgen independent progression. These results are directly relevant to the clinic as a humanized version of PSCA mAb 1GB generated by our laboratory nears application in the clinic.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA439246
Entities
People
- Robert E. Reiter
Organizations
- University of California, Los Angeles