Prostate-specific antigen vaccines for prostate cancer

Abstract

Prostate cancer is the most common malignant tumour in men and there are few treatment options available once the tumour becomes refractory to hormonal manipulation. Prostate-specific antigen (PSA) is a secretory glycoprotein that is commonly expressed by prostatic epithelial cells and is found in elevated levels in the serum of men with prostate cancer. The identification of T cell specific epitopes within the coding sequence of PSA has led to the development of various vaccine strategies that target PSA in an attempt to treat established prostate cancer. These strategies have included human leukocyte antigen-restricted PSA peptides, dendritic cells pulsed with PSA, recombinant viruses expressing PSA and combinations of different vectors. In addition to PSA, several other antigens have been described that may be useful for targeting prostate tumours by vaccines. Animal studies have established the feasibility and safety for many of these agents and clinical trials are now in progress to evaluate the immunological and clinical responses of PSA vaccines. Further research in manipulating anti-PSA immunity with cytokines, costimulatory molecules and other immune modulating agents will likely improve the therapeutic effectiveness of PSA vaccines. Clinical trials designed to evaluate the effects of vaccination in different stages of disease and through different routes of administration need to be performed to define the optimal schedule for PSA vaccines in patients with prostate cancer, or for those at high risk of developing the disease.