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 coup...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2000, Vol.48 (10), p.588-594
Main Authors: ACRES, B, APOSTOLOPOULOS, V, BALLOUL, J.-M, WRESCHNER, D, XING, P.-X, ALI-HADJI, D, BIZOUARNE, N, KIENY, M. P, MCKENZIE, I. F. C
Format: Article
Language:English
Subjects:
Animals
Antibodies, Neoplasm - blood
Antibody response
Antigens
Antineoplastic agents
Biological and medical sciences
Cancer Vaccines - immunology
Cytotoxicity
Fusion protein
Glutathione transferase
Humans
Immune Tolerance
Immunization
Immunological tolerance
Immunotherapy
Interleukin 2
Lymphocytes T
Mannan
Medical sciences
Mice
Mice, Transgenic
MUC-1 antigen
MUC1 gene
Mucin-1 - genetics
Mucin-1 - immunology
Neoplasms, Glandular and Epithelial - therapy
Original
Pharmacology. Drug treatments
T-Lymphocytes, Cytotoxic - immunology
Transgenic animals
Transgenic mice
Vaccination
Vaccines
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Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/PL00006677