MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines |
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Authors: | Bruce Acres Vasso Apostolopoulos Jean-Marc Balloul Danny Wreschner Pei-Xiang Xing Dahlila Ali-Hadji Nadine Bizouarne Marie Paule Kieny Ian FC McKenzie |
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Institution: | (1) Departments of Immunobiology, Molecular Genetics and Molecular and Cellular Biology, Transgène SA, 11 rue de Molsheim, 67082 Strasbourg Cedex, France e-mail: acres@transgene.fr Fax: +33-3-88-27-91-41, FR;(2) Department of Microbiology, Tel Aviv University, Ramat-Amiv, 69978 Tel Aviv, Israel, IL;(3) The Austin Research Institute, Studley Road, Heidelberg, 3084, Victoria, Australia, AU |
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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.
Received: 7 July 1999 / Accepted: 26 August 1999 |
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Keywords: | MUC1 Immunotherapy Transgenic mice Cytotoxic T cells Cancer |
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