Effects of Androgen Ablation on Anti-Tumor Immunity
Abstract
Androgen ablation (AA) constitutes the most common therapy for the treatment of advanced prostate cancer. While initially effective at reducing tumor burden, most patients recur with androgen insensitive disease. There exists a clear need to augment the clinical efficacy of hormone-based therapies, and immunotherapy of prostate cancer represents a promising approach for achieving such augmentation. Moreover, our data indicate that AA affects the immune system both systemically as well as at the prostate. Castration of mice stimulates B and T lymphopoiesis, thymic and bone marrow hyperplasia. The induction of apoptotic cell death following androgen ablation is accompanied by an inflammatory infiltrate comprised predominantly of activated T cells. This AA induced autoimmune-like response exerts limited anti-tumor activity in a mouse prostate cancel model, but the anti-tumor effect is potentially synergistic with CTLA-4 blockade, which promotes the development of autoreactive T cells. We have used the first year of this proposal to obtain and produce all necessary reagents (genes, tumor cell lines, hybridomas, purified antibodies) to position ourselves for studying the effects of AA on prostate cancer immunity as these effects might significantly influence the ability of a tumor-bearing host to mount an effective immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA421972
Entities
People
- W. M. Kast
Organizations
- Loyola University New Orleans