Recombinant viruses as a tool for therapeutic vaccination against human cancers

Viral vectors can be used to express a variety of genes in vivo, that encod e tumor associated antigens, cytokines, or accessory molecules. For vaccina tion pur poses, the ideal viral vector should be safe and enable efficient presentation of expressed antigens to the immune system. It should also exh ibit low intrinsic immunogenicity to allow for its re-administration in ord er to boost relevant specific immune responses. Furthermore, the vector sys tem must meet criteria that enable its industrialization. The characteristi cs of the most promising viral vectors, including retroviruses, poxviruses, adenoviruses, adeno-associated viruses, herpes simplex viruses, and alphav iruses, will be reviewed in this communication. Such recombinant viruses ha ve been successfully used in animal models as therapeutic cancer vaccines. Based on these encouraging results, a series of clinical studies, reviewed herein, have been undertaken. Human clinical trials, have as of today, allo wed investigators to establish that recombinant viruses can be safely used in cancer patients, and that such recombinants call break immune tolerance against tumor-associated antigens. These promising results are now leading to improved immunization protocols associating recombinant viruses with alt ernate antigen-presentation platforms (prime-boost regimens), in order to e licit broad tumor-specific immune responses (humoral and cellular) against multiple target antigens. (C) 2000 Elsevier Science B.V. All rights reserve d.