BACKGROUND: Vaccine targets for prostate cancer have generally been identified either by tissue specific expression in prostate cancer or by assessing immune responses in cancer patients. However, UCSF investigators have taken a novel approach to identify the targets of an immune response in patients who are either responding or not responding to an immune-based treatment (anti-CTLA4 antibody) in a clinical trial at UCSF. CTLA4 blockade with antibody treatment can augment endogenous anti-tumor immunity in animal models and is being developed as an immunotherapy for cancer patients. Defining the antigen-specific responses induced by this treatment can lead to immunological identification of therapeutic targets that may be relevant in prostate cancer patients. These studies provide a unique opportunity to determine the antigen-specific responses that are relevant for immune-mediated clinical responses in prostate cancer, can provide opportunities to predict which patients may respond to therapy, and can provide novel approaches to prostate cancer treatment and vaccination.

DESCRIPTION: UCSF investigators found that immune-mediated clinical responses to CTLA4 blockade is seen in the absence of a specific vaccination, suggesting that endogenous antigen-specific immune responses can be potentiated through this treatment. By focusing on immune responses unique to those patients that responded to immunotherapy, the UCSF investigators were able to identify candidate antigens that correlated with clinical outcome in prostate cancer patients. In addition, a patient’s immune response to the prostate cancer-associated antigens can be used as a diagnostic assay to determine the likelihood that an individual having prostate cancer will exhibit a clinically beneficial response to an immunomodulatory treatment. Furthermore, targeting these antigens with antibodies and/or vaccination may lead to novel therapies for prostate cancer.

One antigen in particular has shown promise because it is expressed at a higher intensity in prostate cancer patients and in prostate cancer cell lines compared to other previously described antigens. Kaplan-Meier survival curves for tumor challenge were plotted for C57BL/6 and FVB mice (5 control and 5 test mice per mouse model) that were immunized with a mouse homolog of the particular antigen. The mice were challenged with Tramp cells or Myc-Cap prostate cancer cells respectively. Immunization with the novel antigen induced anti-tumor responses in both models of prostate cancer.