MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines.
Analyses of MUC1-specific cytotoxic T cell precursor (CTLp) frequencies were performed in mice immunized with three different MUC1 vaccine immunotherapeutic agents. Mice were immunized with either a fusion protein comprising MUC1 and glutathione S-transferase (MUC1-GST), MUC1-GST fusion protein coupled to mannan (MFP) or with a recombinant vaccinia virus expressing both MUC1 and interleukin-2. Mouse strain variations in immune responsiveness have been observed with these vaccines. We have constructed mice transgenic for the human MUC1 gene to study MUC1-specific immune responses and the risk of auto-immunity following MUC1 immunization. Transgenic mice immunized with MUC1 were observed to be partially tolerant in that the MUC1-specific antibody response is lower than that observed in syngeneic but non-transgenic mice. However, a significant MUC1-specific CTLp response to all three vaccines was observed, indicating the ability to overcome T cell, but to a lesser extent B cell, tolerance to MUC1 in these mice. Histological analysis indicates no evidence of auto-immunity to the cells expressing the human MUC1 molecule. These results suggest that it is possible to generate an immune response to a cancer-related antigen without damage to normal tissues expressing the antigen.
Acres
B
B
Department of Immunobiology, Transgène SA, Strasbourg, France. acres@transgene.fr
Apostolopoulos
V
V
Balloul
J M
JM
Wreschner
D
D
Xing
P X
PX
Ali-Hadji
D
D
Bizouarne
N
N
Kieny
M P
MP
McKenzie
I F
IF
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology*; D009375:Neoplasms, Glandular and Epithelial / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D018396:Mucin-1