Prostate cancer: advances in immunotherapy.
The absence of curative therapies for advanced or recurrent forms of prostate cancer has prompted a vigorous search for novel treatment strategies. Immunotherapy encompasses one particularly promising systemic approach to the treatment of prostate cancer. Immune-based strategies for treating prostate cancer have recently been facilitated by the identification of a number of prostate tissue/tumour antigens that can be targeted, either by antibody or T cells, to promote prostate tumour cell injury or death. These same prostate antigens can also be used for the construction of vaccines to induce prostate-specific T cell-mediated immunity. Greater insight into specific mechanisms that govern antigen-specific T cell activation has brought with it a number of innovative methods to induce and enhance T cell-mediated responses against prostate tumours. For instance, autologous dendritic cells loaded with prostate antigens have proved useful to induce prostate-specific T cell activation. Similarly, in vivo manipulations of T cell costimulatory pathway receptors can greatly facilitate tumour-specific T cell activation and potentiate T cell-mediated responses against a number of malignancies, including prostate cancer. For example, blocking T cell cytotoxic lymphocyte-associated antigen 4 (CTLA-4) receptor binding to its ligand prevents the down-regulation of T cell responses and can even potentiate T cell antitumoural immunity in mouse models of prostate cancer. Androgen ablation (AA) may induce prostate tumour/tissue-specific T cell mediated inflammation and, as such, a phase II trial is currently in progress to ascertain whether CTLA-4 blockade can enhance AA-induced treatment responses in patients with advanced prostate cancer. Nevertheless, further basic and clinical investigation is still required to establish immunotherapy as a true prostate cancer treatment option.
Hurwitz
Arthur A
AA
Department of Microbiology, SUNY Upstate Medical University, Syracuse, NY, USA.
Yanover
Paul
P
Markowitz
Mary
M
Allison
James P
JP
Kwon
Eugene D
ED
D000728:Androgens / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use; D016207:Cytokines / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D000728:Androgens; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell