Publications & Reports

MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines.

Acres B, Apostolopoulos V, Balloul JM, Wreschner D, Xing PX, Ali-Hadji D, Bizouarne N, Kieny MP, McKenzie IF
Department of Immunobiology, Transgene SA, Strasbourg, France. acres@transgene.fr

Abstract

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.

Publication

  • Journal: Cancer Immunology Immunotherapy
  • Published: 01/01/2000
  • Volume: 48
  • Issue: 10
  • Pagination: 588-594