Adenoviral delivery of B7-1 (CD80) increases the immunogenicity of human ovarian and cervical carcinoma cells.
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.
Gilligan
M G
MG
CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, UK.
Knox
P
P
Weedon
S
S
Barton
R
R
Kerr
D J
DJ
Searle
P
P
Young
L S
LS
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
D018122:B7-1 Antigen