Abstract
Enhanced immunogenicity has been reported following transfection of a variety of immunogenic tumors with the B7.1 co-stimulatory molecule. The purpose of the present study was to determine if transfection of a weakly immunogenic rat brain tumor, the F98 glioma, with the gene encoding B7.1 could enhance its immunogenicity. F98 cells were transfected with a plasmid containing the B7.1 gene, and stable transfectants (F98/B7.1) were obtained. Flow cytometric analysis confirmed the expression of B7.1 and MHC class I antigens on the cell surface. To investigate the effects of B7.1 expression on the tumorigenicity of the F98 glioma, Fischer rats were implanted intracerebrally with either F98 (wild-type) or F98/B7.1 transfected cells. No significant differences in survival times were noted. Mean survival times of 21.8 and 24.0 days were observed for the respective groups at a challenge dose of 103 cells. These differences in survival time were not significant. To determine if expression of B7.1 enhanced the immunogenicity of the F98 glioma, rats were vaccinated weekly for 3 weeks with 107 mitomycin C-treated F98 or F98/B7.1 cells injected subcutaneously and then challenged intracerebrally with F98 cells 1 week later. Unvaccinated animals or those that received wild-type F98 cells as a vaccine had a survival time (mean ± s.d.) of 22.3 ± 1.5 days following tumor challenge versus 20.0 ± 1.7 days for rats that had been vaccinated with F98/B7.1. Although we recognize that it might be possible to design more effective vaccination regimes, nevertheless, our data indicate that transfection of the B7.1 gene into the F98 rat glioma did not enhance its immunogenicity, and that other approaches will be required.
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Acknowledgements
David B Paul was supported by the National Cancer Institute, National Research Service Award CA-09338, Division of Cancer Prevention and Control and the research was supported by a Board of Regents Targeted Interdisciplinary Seed Grant, Office of Research, The Ohio State University and The Ohio State University Comprehensive Cancer Center.
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Paul, D., Barth, R., Yang, W. et al. B7.1 expression by the weakly immunogenic F98 rat glioma does not enhance immunogenicity. Gene Ther 7, 993–999 (2000). https://doi.org/10.1038/sj.gt.3301209
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DOI: https://doi.org/10.1038/sj.gt.3301209
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