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Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes
A number of cell surface molecules with specificity to tumour cells have been identified and monoclonal antibodies (mAb) to some of these antigens have been used for targeting tumour cells in vivo. We have sought to link the powerful effector mechanisms of cytotoxic T-cells with the specificity of m...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2000
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374430/ https://www.ncbi.nlm.nih.gov/pubmed/10737389 http://dx.doi.org/10.1054/bjoc.1999.1042 |
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author | Ogg, G S Dunbar, P R Cerundolo, V McMichael, A J Lemoine, N R Savage, P |
author_facet | Ogg, G S Dunbar, P R Cerundolo, V McMichael, A J Lemoine, N R Savage, P |
author_sort | Ogg, G S |
collection | PubMed |
description | A number of cell surface molecules with specificity to tumour cells have been identified and monoclonal antibodies (mAb) to some of these antigens have been used for targeting tumour cells in vivo. We have sought to link the powerful effector mechanisms of cytotoxic T-cells with the specificity of mAb, by targeting recombinant HLA class I molecules to tumour cells using an antibody delivery system. Soluble recombinant MHC class I/peptide complexes including HLA-A2.1 refolded around an immunodominant peptide from the HIV gag protein (HLA-A2/gag) were synthesized, and the stability of these complexes at 37°C was confirmed by enzyme-linked immunosorbent assay using a conformation-specific antibody. MHC class I-negative lymphoma cells (Daudi) were labelled with a biotinylated mAb specific for a cell surface protein (anti-CD20) then linked to soluble biotinylated HLA-A2/gag complexes using an avidin bridge. Flow cytometry revealed strong labelling of lymphoma cells with HLA-A2/gag complexes (80-fold increase in mean channel fluorescence). CTL specific for HLA-A2/gag efficiently lysed complex-targeted cells, while control CTL (specific for an HLA-A2.1-restricted epitope of melan-A) did not. Similarly, SK-mel-29 melanoma cells were also efficiently lysed by HLA-A2/gag-specific CTL when HLA-A2/gag complexes were linked to their surface via the HMW-MAA specific anti-melanoma antibody 225.28s. With further consideration to the in vivo stability of the MHC class I/peptide complexes, this system could prove a new strategy for the immunological therapy of cancer. © 2000 Cancer Research Campaign |
format | Text |
id | pubmed-2374430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23744302009-09-10 Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes Ogg, G S Dunbar, P R Cerundolo, V McMichael, A J Lemoine, N R Savage, P Br J Cancer Regular Article A number of cell surface molecules with specificity to tumour cells have been identified and monoclonal antibodies (mAb) to some of these antigens have been used for targeting tumour cells in vivo. We have sought to link the powerful effector mechanisms of cytotoxic T-cells with the specificity of mAb, by targeting recombinant HLA class I molecules to tumour cells using an antibody delivery system. Soluble recombinant MHC class I/peptide complexes including HLA-A2.1 refolded around an immunodominant peptide from the HIV gag protein (HLA-A2/gag) were synthesized, and the stability of these complexes at 37°C was confirmed by enzyme-linked immunosorbent assay using a conformation-specific antibody. MHC class I-negative lymphoma cells (Daudi) were labelled with a biotinylated mAb specific for a cell surface protein (anti-CD20) then linked to soluble biotinylated HLA-A2/gag complexes using an avidin bridge. Flow cytometry revealed strong labelling of lymphoma cells with HLA-A2/gag complexes (80-fold increase in mean channel fluorescence). CTL specific for HLA-A2/gag efficiently lysed complex-targeted cells, while control CTL (specific for an HLA-A2.1-restricted epitope of melan-A) did not. Similarly, SK-mel-29 melanoma cells were also efficiently lysed by HLA-A2/gag-specific CTL when HLA-A2/gag complexes were linked to their surface via the HMW-MAA specific anti-melanoma antibody 225.28s. With further consideration to the in vivo stability of the MHC class I/peptide complexes, this system could prove a new strategy for the immunological therapy of cancer. © 2000 Cancer Research Campaign Nature Publishing Group 2000-03 2000-02-01 /pmc/articles/PMC2374430/ /pubmed/10737389 http://dx.doi.org/10.1054/bjoc.1999.1042 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 Ogg, G S Dunbar, P R Cerundolo, V McMichael, A J Lemoine, N R Savage, P Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes |
title | Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes |
title_full | Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes |
title_fullStr | Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes |
title_full_unstemmed | Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes |
title_short | Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes |
title_sort | sensitization of tumour cells to lysis by virus-specific ctl using antibody-targeted mhc class i/peptide complexes |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374430/ https://www.ncbi.nlm.nih.gov/pubmed/10737389 http://dx.doi.org/10.1054/bjoc.1999.1042 |
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