Prospects and limitations of recombinant poxviruses for prostate cancer immunotherapy.
Prostate cancer is a disease that may be amenable to immunotherapy approaches, as evidenced by the ability to induce human cytotoxic immune responses against prostate cancer cells. Recent interest in recombinant poxvirus vaccines coupled with the need for new prostate cancer therapies has led to the development of several recombinant poxvirus agents designed for prostate cancer treatment. Whether these agents will be effective in treating prostate cancer is under investigation in several ongoing and upcoming clinical trials. In the meantime, data from preclinical tumor models have provided information that may aid in improving recombinant poxviruses for clinical use. While animal studies have shown the ability of recombinant poxvirus vaccination to induce an immune response that protects against lethal tumor, these antitumor effects are variable and depend on a number of factors. Co-expression of immunomodulating gene products, such as cytokines and costimulatory molecules, have been shown to influence antitumor immunity; in fact, cytokine delivery alone can be enough to protect against tumor-related death. Patterns and levels of recombinant antigen expression also affect the immune response to that antigen, as seen by studies of various poxvirus promoters and cell compartment-targeting sequences. In addition, vaccine strategies targeting self-antigens have shown that immunological tolerance can negatively impact the induction of antitumor and antigen-specific immunity. Although vaccinia virus has been most intensely studied thus far, other poxviruses, including fowlpox and canarypox, are also promising vaccine candidates. These alternative vectors may circumvent some of the disadvantages associated with vaccinia virus, such as pre-existing vaccinia immunity. A deeper understanding of these factors and others that impact the development of antitumor immunity will be necessary to guide the development of recombinant poxviruses for prostate cancer therapy.
Hwang
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Department of Surgery/Urology, University of Michigan School of Medicine, Ann Arbor 48109, USA. hwanga@umich.edu
Sanda
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D000914:Antibodies, Viral; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; D004274:DNA, Recombinant; D011993:Recombinant Fusion Proteins; D012900:Smallpox Vaccine; D014765:Viral Vaccines