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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 beta-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.

Original publication

DOI

10.1038/sj.gt.3300672

Type

Journal article

Journal

Gene Ther

Publication Date

07/1998

Volume

5

Pages

965 - 974

Keywords

Adenoviridae, B7-1 Antigen, Coculture Techniques, Female, Gene Expression, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Humans, Lymphocyte Activation, Ovarian Neoplasms, T-Lymphocytes, Time Factors, Tumor Cells, Cultured, Uterine Cervical Neoplasms