A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1

MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 b...

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Autores principales: Wilkinson, R W, Ross, E L, Lee-MacAry, A E, Laylor, R, Burchell, J, Taylor-Papadimitriou, J, Snary, D
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Regular Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363579/
https://www.ncbi.nlm.nih.gov/pubmed/11027434
http://dx.doi.org/10.1054/bjoc.2000.1431
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author Wilkinson, R W
Ross, E L
Lee-MacAry, A E
Laylor, R
Burchell, J
Taylor-Papadimitriou, J
Snary, D
author_facet Wilkinson, R W
Ross, E L
Lee-MacAry, A E
Laylor, R
Burchell, J
Taylor-Papadimitriou, J
Snary, D
author_sort Wilkinson, R W
collection PubMed
description MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 binds the linear core protein sequence, PDTR, contained within the immunodominant domain of the tandem repeat of MUC1. The efficacy of murine and humanized HMFG1 (Ab1) used as an anti-idiotypic vaccine was examined in mice transgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour cells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody inoculations in the presence of adjuvant. Impaired tumour growth at day 35 and highest Ab3 levels were found in mice that had received mHMFG1 with RAS adjuvant. However, comparison of Ab3 levels in individual mice with tumour size in all treatment groups did not show a correlation between smaller tumours and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mechanisms. © 2000 Cancer Research Campaign
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spelling pubmed-23635792009-09-10 A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1 Wilkinson, R W Ross, E L Lee-MacAry, A E Laylor, R Burchell, J Taylor-Papadimitriou, J Snary, D Br J Cancer Regular Article MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 binds the linear core protein sequence, PDTR, contained within the immunodominant domain of the tandem repeat of MUC1. The efficacy of murine and humanized HMFG1 (Ab1) used as an anti-idiotypic vaccine was examined in mice transgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour cells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody inoculations in the presence of adjuvant. Impaired tumour growth at day 35 and highest Ab3 levels were found in mice that had received mHMFG1 with RAS adjuvant. However, comparison of Ab3 levels in individual mice with tumour size in all treatment groups did not show a correlation between smaller tumours and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mechanisms. © 2000 Cancer Research Campaign Nature Publishing Group 2000-11 /pmc/articles/PMC2363579/ /pubmed/11027434 http://dx.doi.org/10.1054/bjoc.2000.1431 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Wilkinson, R W
Ross, E L
Lee-MacAry, A E
Laylor, R
Burchell, J
Taylor-Papadimitriou, J
Snary, D
A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
title A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
title_full A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
title_fullStr A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
title_full_unstemmed A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
title_short A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1
title_sort transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human muc1
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363579/
https://www.ncbi.nlm.nih.gov/pubmed/11027434
http://dx.doi.org/10.1054/bjoc.2000.1431
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