TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets
Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time d...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/586314 |
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| _version_ | 1832553170999443456 |
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| author | Trudy Straetemans Mandy van Brakel Sabine van Steenbergen Marieke Broertjes Joost Drexhage Joost Hegmans Bart N. Lambrecht Cor Lamers Pierre van Der Bruggen Pierre G. Coulie Reno Debets |
| author_facet | Trudy Straetemans Mandy van Brakel Sabine van Steenbergen Marieke Broertjes Joost Drexhage Joost Hegmans Bart N. Lambrecht Cor Lamers Pierre van Der Bruggen Pierre G. Coulie Reno Debets |
| author_sort | Trudy Straetemans |
| collection | DOAJ |
| description | Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2) and MAGE-A3243-258/HLA-DP4 (MA3/DP4). We molecularly characterized TCRαβ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial. |
| format | Article |
| id | doaj-art-12890943695641fe9d079b8f6d04f558 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-12890943695641fe9d079b8f6d04f5582025-02-03T05:54:40ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/586314586314TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune TargetsTrudy Straetemans0Mandy van Brakel1Sabine van Steenbergen2Marieke Broertjes3Joost Drexhage4Joost Hegmans5Bart N. Lambrecht6Cor Lamers7Pierre van Der Bruggen8Pierre G. Coulie9Reno Debets10Laboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsLaboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsLaboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsLaboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsLaboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsDepartment of Pulmonary Diseases, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsDepartment of Pulmonary Diseases, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsLaboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsLudwig Institute for Cancer Research Ltd, Brussels Branch, and de Duve Institute, Université Catholique de Louvain, 1200 Brussels, BelgiumLudwig Institute for Cancer Research Ltd, Brussels Branch, and de Duve Institute, Université Catholique de Louvain, 1200 Brussels, BelgiumLaboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The NetherlandsAdoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2) and MAGE-A3243-258/HLA-DP4 (MA3/DP4). We molecularly characterized TCRαβ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial.http://dx.doi.org/10.1155/2012/586314 |
| spellingShingle | Trudy Straetemans Mandy van Brakel Sabine van Steenbergen Marieke Broertjes Joost Drexhage Joost Hegmans Bart N. Lambrecht Cor Lamers Pierre van Der Bruggen Pierre G. Coulie Reno Debets TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets Clinical and Developmental Immunology |
| title | TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets |
| title_full | TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets |
| title_fullStr | TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets |
| title_full_unstemmed | TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets |
| title_short | TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets |
| title_sort | tcr gene transfer mage c2 hla a2 and mage a3 hla dp4 epitopes as melanoma specific immune targets |
| url | http://dx.doi.org/10.1155/2012/586314 |
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