Abstract
The majority of tumour cells do not express immune costimulatory molecules and this may account for their inability to stimulate directly an antitumour T cell response. Here we report on the construction of a recombinant E1/E3-deleted adenovirus encoding the human B7–1 costimulatory molecule. We explored the use of this vector for gene transfer to a number of human ovarian and cervical tumour cell lines, and to primary ovarian tumour material. Rapid and efficient gene transfer and expression was obtained in the majority of cases using a multiplicity of infection of 30 plaque forming units per cell. B7–1 expression was detectable at the cell surface within 12 h and was still detectable 10 days after infection. The immunogenicity of gene-modified tumour cells was tested in an allogeneic mixed lymphocyte tumour cell culture. Tumour cells expressing B7–1 were found to induce significantly higher levels of T cell proliferation than tumour cells modified with a control adenovirus carrying the β-galactosidase gene. B7–1-induced T cell proliferation could be blocked by the addition of anti-B7–1 antibodies at the initiation of cocultures. These results support the rationale for use of adenovirally delivered B7–1 for genetic immunotherapy of ovarian and cervical cancer.
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Gilligan, M., Knox, P., Weedon, S. et al. Adenoviral delivery of B7–1 (CD80) increases the immunogenicity of human ovarian and cervical carcinoma cells. Gene Ther 5, 965–974 (1998). https://doi.org/10.1038/sj.gt.3300672
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DOI: https://doi.org/10.1038/sj.gt.3300672
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