Expression of co-stimulatory molecules by tumor cells decreases tumorigenicity but may also reduce systemic antitumor immunity.
Many tumor cells do not express co-stimulatory molecules, and this may account, in part, for their poor ability to stimulate T cells directly. One strategy to enhance immune recognition would be to express such molecules on the tumor cell. Here, we show that expression of a member of the B7 family of co-stimulatory molecules by CMT93 murine colorectal tumor or 1735 murine melanoma cells resulted in a local antitumor response in immunocompetent mice. The antitumor effect was diminished in athymic nude mice, indicating that T cells played an important part in this response. The ability of the B7-expressing tumor cells to generate systemic protective immunity was investigated by excision of tumors that developed from the initial inoculation followed by rechallenge with parental tumor cells. CMT93 is a poorly immunogenic tumor and no significant systemic immunity was elicited by the expression of B7-1 in these cells. 1735 melanoma is a mildly immunogenic tumor. Unexpectedly, the systemic immunity obtained with 1735 tumors expressing B7-1 or B7-2 was weaker than that generated by parental 1735 cells (p < 0.001, stratified logrank test), even when coexpression of interferon-gamma in the B7-1 cells produced high levels of surface MHC class I expression. These results suggest that some caution is appropriate when considering the use of these molecules in the gene therapy of cancer.
Chong
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Imperial Cancer Research Fund Laboratory of Cancer Gene Therapy, Rayne Institute, St. Thomas' Hospital, London, UK.
Hutchinson
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G
Hart
I R
IR
Vile
R G
RG
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D002455:Cell Division; D015179:Colorectal Neoplasms; D005822:Genetic Vectors / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics; D008545:Melanoma; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D007371:Interferon-gamma