Expression of B7.1 in a MUC1-expressing mouse mammary epithelial tumour cell line inhibits tumorigenicity but does not induce autoimmunity in MUC1 transgenic mice.
The MUC1 epithelial mucin, which is overexpressed and aberrantly glycosylated in breast and other carcinomas, is also expressed on the apical surface of most normal glandular epithelial cells. Since clinical trials evaluating the efficacy of MUC1-based vaccines have been initiated in breast cancer patients, it is important to address the question of whether an effective immune response to the cancer associated mucin can be generated without inducing autoimmunity. Since non-classic cytotoxic T lymphocyte (CTL) responses to MUC1 have been reported, it is also relevant to examine the role of costimulatory molecules in the effective presentation of MUC1 based antigens. We have therefore looked at the effect of expressing B7.1 on the tumorigenicity of a MUC1 expressing mammary epithelial cell line (410.4) in a transgenic mouse expressing MUC1 on its normal glandular epithelial tissues. Coexpression of B7.1 with MUC1 in 410. 4 cells resulted in a dramatic inhibition of tumour growth which depended on the activity of CD4+ and CD8+ T cells. The epithelial tissues in the transgenic mice able to reject the B7.1, MUC1-expressing tumours showed no evidence of degeneration and the mice survived their normal life span. The results demonstrate that an immune response to the MUC1 antigen can be induced in MUC1 transgenic mice and that presentation of the antigen, whether directly or by cross-priming, is markedly enhanced by coexpression of B7.1.
Smith
M
M
Imperial Cancer Research Fund, London, UK.
Burchell
J M
JM
Graham
R
R
Cohen
E P
EP
Taylor-Papadimitriou
J
J
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000378:metabolism*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D018396:Mucin-1; D009363:Neoplasm Proteins