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 wer e performed in mice immunized with three different MUC1 vaccine immunothera peutic agents. Mice were immunized with either a fusion protein comprising MUC1 and glutathione S-transferase (MUC1-GST), MUC1-GST fusion protein coup led to mannan (MFP) or with a recombinant vaccinia virus expressing both MU C1 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 o f auto-immunity following MUC1 immunization. Transgenic mice immunized with MUC1 were observed to be partially tolerant in that the MUC1-specific anti body response is lower than that observed in syngeneic but non-transgenic m ice. However, a significant MUC1-specific CTLp response to all three vaccin es was observed, indicating the ability to overcome T cell, but to a lesser extent B cell, tolerance to MUC1 in these mice. Histological analysis indi cates no evidence of auto-immunity to the cells expressing the human MUC1 m olecule. These results suggest that it is possible to generate an immune re sponse to a cancer-related antigen without damage to normal tissues express ing the antigen.