ABSTRACT
In contrast to the success of many prophylactic vaccines, therapeutic vaccination for established chronic infections as well as cancer has yet to achieve widespread acceptance. To date, no therapeutic vaccine has been approved for general use in the United States, despite there being a number that have recently been tested in Phase III registration trials. The striking differences in success between immunoprophylaxis and immunotherapy are based on the fact that, in order to become successfully established within the host, either pathogens or cancer cells have developed mechanisms to avoid recognition and elimination by the immune system (Table 1). Potential mechanisms for immune invasion are best understood for tumors and viruses, which often use common strategies. Downmodulation of components of the antigen processing and presentation system to T cells represents one of the best defined mechanisms for both viruses and tumors [1-31]. Production of cytokines that inhibit or divert productive effector responses [32-35] as well as induction of antigenspecific tolerance through normal pathways of selftolerance generation [36-46] represents additional mechanisms by which tumors and some viruses can avoid recognition by the immune system. However, these mechanisms of immune resistance do not represent absolute barriers. Most chronic viral infections involve expression of at least one viral gene which provides a target for immunotherapy. Although they are derived from “self,” all tumors express antigens recognizable by the immune system, either as unique antigens (the result of genetic alterations), tissue-specific antigens or upregulated self-antigens (Table 2) [47,48]. While most successful prophylactic vaccines protect through the induction of long-lived neutralizing antibody responses, successful immunotherapy of established cancer or pathogenic infections will likely depend to a larger extent upon diverse effector pathways regulated by both CD4 and CD8 T cells [49].
