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

Bruce Acres, Vasso Apostolopoulos, Jean Mare Balloul, Danny Wreschner, Pei Xiang Xing, Dahlila Ali-Hadji, Nadine Bizouarne, Marie Paule Kieny, Ian F.C. McKenzie

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)588-594
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume48
Issue number10
DOIs
StatePublished - 2000

Keywords

  • Cancer
  • Cytotoxic T cells
  • Immunotherapy
  • MUC1
  • Transgenic mice

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