Recombinant Vaccinia Virus Vaccine against the Human Melanoma Antigen p97 for Use in Immunotherapy

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-02, Vol.85 (4), p.1052-1056
• Main Authors: Estin, Charles D., Stevenson, Ulrike S., Plowman, Gregory D., Hu, Shiu-Lok, Sridhar, Pennathur, Hellström, Ingegerd, Brown, Joseph P., Hellström, Karl Erik
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Neoplasm - biosynthesis; Antigens; Antigens - therapeutic use; Antigens, Neoplasm - immunology; Antigens, Neoplasm - therapeutic use; Biological and medical sciences; Cell lines; Female; Fundamental and applied biological sciences. Psychology; Immune response; Immunity, Cellular; Immunization; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lungs; Lymphocytes; Macaca fascicularis - immunology; Male; Melanoma - immunology; Melanoma, Experimental - immunology; Melanoma, Experimental - secondary; Melanoma, Experimental - therapy; Melanoma-Specific Antigens; Mice; Mice, Inbred C3H; Microbiology; Neoplasm Proteins - immunology; Neoplasm Proteins - therapeutic use; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; Tumors; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; vaccinia virus; Vaccinia virus - genetics; Virology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.4.1052

We have constructed a recombinant vaccinia virus, v-p97NY, which expresses the human melanoma-associated glycoprotein p97. Immunization with v-p97NY could induce humoral and cell-mediated immunity to p97, including delayed-type hypersensitivity, in mice and in two of two monkeys (Macaca fascicularis). The fact that an immune response was induced also in monkeys is important because normal cells from monkeys, but not from mice, express a low level of cross-reactive p97. Mice immunized with v-p97NY rejected transplants of syngeneic mouse melanoma expressing p97. A rejection response could be detected also when immunization was started 2 days after tumor transplantation, irrespective of whether the transplanted cells grew subcutaneously or as lung metastases. Evidence was obtained that melanoma cells lacking p97 may be killed as ``bystanders'' at the site of an immune response to melanoma cells expressing p97.