<abstract xmlns="http://www.w3.org/1999/xhtml">Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1+ metastatic tumour, DA3-MUC1 because, unlike many MUC1+ tumour models, DA3-MUC1 is not spontaneously rejected in mice making it an alternative model for immunotherapy studies. Further, DA3-MUC1 cells are resistant to lysis by anti-MUC1 cytotoxic T cells (CTLs). The inability of DA3-MUC1 tumours to be rejected in naïve mice as well as vaccination to MUC1 was attributed to a deficiency of expression of MHC class I molecules on the tumour cell surface. <italic>In vitro</italic> and <italic>in vivo</italic> analysis of subcutaneous tumours and lung metastases demonstrated that DA3-MUC1 tumour cells have a low expression (&lt; 6%) of MHC class I which can be upregulated (> 90%) following culturing with IFN-γ. Results from flow cytometry analysis and immunoperoxidase staining indicated that the <italic>in vitro</italic> up-regulation of MHC class I could be maintained for up to seven days <italic>in vivo</italic>, without affecting the expression levels of MUC1 antigen. Interestingly, MUC1-specific CTL that lyse DA3-MUC1 targets <italic>in vitro</italic> were induced in MFP immunised mice but failed to protect mice from a DA3-MUC1 tumour challenge. These results highlight the importance of MHC class I molecules in the induction of anti-tumour immunity and the MFP immune response.</abstract>

Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1+ metastatic tumour, DA3-MUC1 because, unlike many MUC1+ tumour models, DA3-MUC1 is not spontaneously rejected in mice making it an alternative model for immunotherapy studies. Further, DA3-MUC1 cells are resistant to lysis by anti-MUC1 cytotoxic T cells (CTLs). The inability of DA3-MUC1 tumours to be rejected in naïve mice as well as vaccination to MUC1 was attributed to a deficiency of expression of MHC class I molecules on the tumour cell surface. In vitro and in vivo analysis of subcutaneous tumours and lung metastases demonstrated that DA3-MUC1 tumour cells have a low expression (< 6%) of MHC class I which can be upregulated (> 90%) following culturing with IFN-γ. Results from flow cytometry analysis and immunoperoxidase staining indicated that the in vitro up-regulation of MHC class I could be maintained for up to seven days in vivo, without affecting the expression levels of MUC1 antigen. Interestingly, MUC1-specific CTL that lyse DA3-MUC1 targets in vitro were induced in MFP immunised mice but failed to protect mice from a DA3-MUC1 tumour challenge. These results highlight the importance of MHC class I molecules in the induction of anti-tumour immunity and the MFP immune response.

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Current Address, Echuca Regional Health, Echuca VIC Australia

Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel

Current Address, Emeritus Professor, University of Melbourne, VIC Australia

Bio-organic and Medicinal Chemistry Laboratory, Burnet Institute, VIC Australia

Department of Pathology, University of Melbourne, Parkville, Victoria, Australia

Department of Immunology, Monash University, Melbourne, Victoria, Australia

Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, VIC Australia

PRILOZI

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1+ metastatic tumour, DA3-MUC1 because, unlike many MUC1+ tumour models, DA3-MUC1 is not spontaneously rejected in mice making it an alternative model for immunotherapy studies. Further, DA3-MUC1 cells are resistant to lysis by anti-MUC1 cytotoxic T cells (CTLs). The inability of DA3-MUC1 tumours to be rejected in naïve mice as well as vaccination to MUC1 was attributed to a deficiency of expression of MHC class I molecules on the tumour cell surface. In vitro and in vivo analysis of subcutaneous tumours and lung metastases demonstrated that DA3-MUC1 tumour cells have a low expression ( 90%) following culturing with IFN-γ. Results from flow cytometry analysis and immunoperoxidase staining indicated that the in vitro up-regulation of MHC class I could be maintained for up to seven days in vivo, without affecting the expression levels of MUC1 antigen. Interestingly, MUC1-specific CTL that lyse DA3-MUC1 targets in vitro were induced in MFP immunised mice but failed to protect mice from a DA3-MUC1 tumour challenge. These results highlight the importance of MHC class I molecules in the induction of anti-tumour immunity and the MFP immune response.

Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1+ metastatic tumour, DA3-MUC1 because, unlike many...

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Pubblicato online: 15 lug 2016

Pagine: 15 - 25

DOI: https://doi.org/10.1515/prilozi-2016-0001

Parole chiave
MUC1. MHC class I, interferon-gamma, tumour, immunotherapy

© 2016 Catherine J. Lees et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Pubblicato online: 15 lug 2016

Pagine: 15 - 25

DOI: https://doi.org/10.1515/prilozi-2016-0001

Parole chiaveMUC1. MHC class I, interferon-gamma, tumour, immunotherapy

© 2016 Catherine J. Lees et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Parole chiave
MUC1. MHC class I, interferon-gamma, tumour, immunotherapy