TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets

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

doi:10.1155/2012/586314

TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets

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

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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-C2 336-344/HLA-A2 (MC2/A2) and MAGE-A3 243-258/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. Copyright 2012 Trudy Straetemans et al.

Original language	English
Journal	Clinical & Developmental Immunology
Volume	2012
DOIs	https://doi.org/10.1155/2012/586314
Publication status	Published - 19 Mar 2012
Externally published	Yes

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title = "TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets",

abstract = "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-C2 336-344/HLA-A2 (MC2/A2) and MAGE-A3 243-258/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. Copyright 2012 Trudy Straetemans et al.",

author = "Trudy Straetemans and {Van Brakel}, Mandy and {Van Steenbergen}, Sabine and Marieke Broertjes and Joost Drexhage and Joost Hegmans and Lambrecht, {Bart N.} and Cor Lamers and Bruggen, {Pierre Van Der} and Coulie, {Pierre G.} and Reno Debets",

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doi = "10.1155/2012/586314",

language = "English",

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AU - Straetemans, Trudy

AU - Van Brakel, Mandy

AU - Van Steenbergen, Sabine

AU - Broertjes, Marieke

AU - Drexhage, Joost

AU - Hegmans, Joost

AU - Lambrecht, Bart N.

AU - Lamers, Cor

AU - Bruggen, Pierre Van Der

AU - Coulie, Pierre G.

AU - Debets, Reno

PY - 2012/3/19

Y1 - 2012/3/19

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AB - 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-C2 336-344/HLA-A2 (MC2/A2) and MAGE-A3 243-258/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. Copyright 2012 Trudy Straetemans et al.

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TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets

Abstract

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