期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：23
页码：9498-9502
DOI：10.1073/pnas.87.23.9498
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts.
