Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
ANTITUMOR VACCINES: III. RECOMBINANT VACCINIA VIRUS AS AN APPROACH TO TUMOR IMMUNOTHERAPY
New Generation Vaccines. Woodrow GC and Levine MM, eds. New York, Marcel Dekker, p. 870-7, 1990.. Unique Identifier : AIDSLINE ICDB/92678618 Hu SL; Hellstrom I; Hellstrom KE; Dept. of Virology, ONCOGEN, Seattle, WA
Abstract:
Use of recombinant vaccinia virus in prophylaxis and immunotherapy of neoplastic diseases has important potential advantages, including (1) recombinant vaccinia virus contains a defined tumor antigen, making it easier to obtain specific and reproducible results; (2) the tumor antigen is expressed in the context of viral infection, which allows the copresentation of tumor antigen with host histocompatibility antigens and with highly immunogenic vaccinia virus proteins, which may serve as potential adjuvants; and (3) this approach has been used successfully to develop vaccines against various infectious diseases. Recombinants expressing viral-encoded or oncogene-encoded antigens and a recombinant vaccinia virus expressing a human tumor-associated differentiation antigen (TADA) are reviewed. Recombinant vaccinia vaccines elicit not only humoral, but cell-mediated immunity, which is of critical importance in tumor immunotherapy. Several examples exist in which recombinant vaccinia virus was employed for tumor prophylaxis and immunotherapy, including recombinants expressing the envelope antigens of Friend murine leukemia virus, T antigens of polyoma virus, the rat neu oncogene product, and the human melanoma-associated antigen. Experiments were conducted in which the p97 tumor antigen was used as a target for making a recombinant virus. P97 is a monoclonal antibody-defined human melanoma TADA, which has been cloned and sequenced in its entirety. A recombinant vaccinia virus, v-p97NY, was prepared by introducing the cloned p97 gene into the vaccinia virus genome. V-97NY is immunogenic in mice; immunization with v-p97NY induces antitumor activity in mice; and v-p97NY is immunogenic in monkeys. Studies in which human cancer patients were given MAb to TADA have suggested that an immune response to TADA can be induced and may correlate with a favorable prognosis. Much more work needs to be done to demonstrate the safety and efficacy of live recombinant vaccinia virus in clinical studies and to understand the immunological mechanisms involved in tumor rejection. (29 Refs)
Keywords: Animal Antibodies, Neoplasm/BIOSYNTHESIS Antigens, Neoplasm/*GENETICS/*IMMUNOLOGY Cloning, Molecular Human Immunotherapy, Active Macaca fascicularis Melanoma/IMMUNOLOGY/THERAPY Mice Neoplasm Proteins/GENETICS/IMMUNOLOGY Neoplasms/*IMMUNOLOGY/*THERAPY Recombination, Genetic/GENETICS Skin Neoplasms/IMMUNOLOGY/THERAPY Transfection/GENETICS Vaccines, Synthetic/*ADMINISTRATION & DOSAGE/*IMMUNOLOGY Vaccinia Virus/*GENETICS/*IMMUNOLOGY MONOGRAPH 920430
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
