title: Adenoviral delivery of B7-1 (CD80) increases the immunogenicity of human ovarian and cervical carcinoma cells.
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 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.
authors.affiliation: CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Gilligan
authors.forename: P
authors.initials: P
authors.lastname: Knox
authors.forename: S
authors.initials: S
authors.lastname: Weedon
authors.forename: R
authors.initials: R
authors.lastname: Barton
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: P
authors.initials: P
authors.lastname: Searle
authors.forename: L S
authors.initials: LS
authors.lastname: Young
mesh_terms: D000256:Adenoviridae; D018122:B7-1 Antigen / Q000235:genetics*; D018920:Coculture Techniques; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy
chemical_list: D018122:B7-1 Antigen