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

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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 TCR alpha beta 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-V alpha 3/V beta 28 and TCR-V alpha 38/V beta 2 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.
Keywords
MAGE-A, METASTATIC MELANOMA, TUMOR-SPECIFIC RECEPTORS, CD4(+) T-CELLS, DENDRITIC CELLS, LUNG-CANCER, ADOPTIVE IMMUNOTHERAPY, ANTIGENIC PEPTIDES, ADVERSE EVENT, SINGLE-CHAIN

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Chicago
Straetemans, Trudy, Mandy van Brakel, Sabine van Steenbergen, Marieke Broertjes, Joost Drexhage, Joost Hegmans, Bart Lambrecht, et al. 2012. “TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-specific Immune Targets.” Clinical & Developmental Immunology.
APA
Straetemans, T., van Brakel, M., van Steenbergen, S., Broertjes, M., Drexhage, J., Hegmans, J., Lambrecht, B., et al. (2012). TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets. CLINICAL & DEVELOPMENTAL IMMUNOLOGY.
Vancouver
1.
Straetemans T, van Brakel M, van Steenbergen S, Broertjes M, Drexhage J, Hegmans J, et al. TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets. CLINICAL & DEVELOPMENTAL IMMUNOLOGY. 2012;
MLA
Straetemans, Trudy, Mandy van Brakel, Sabine van Steenbergen, et al. “TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-specific Immune Targets.” CLINICAL & DEVELOPMENTAL IMMUNOLOGY (2012): n. pag. Print.
@article{2085107,
  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 {\textacutedbl}on-target{\textacutedbl} 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 TCR alpha beta 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-V alpha 3/V beta 28 and TCR-V alpha 38/V beta 2 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.},
  articleno    = {586314},
  author       = {Straetemans, Trudy and van Brakel, Mandy and van Steenbergen, Sabine and Broertjes, Marieke and Drexhage, Joost and Hegmans, Joost and Lambrecht, Bart and Lamers, Cor and van der Bruggen, Pierre and Coulie, Pierre G and Debets, Reno},
  issn         = {1740-2522},
  journal      = {CLINICAL \& DEVELOPMENTAL IMMUNOLOGY},
  keyword      = {MAGE-A,METASTATIC MELANOMA,TUMOR-SPECIFIC RECEPTORS,CD4(+) T-CELLS,DENDRITIC CELLS,LUNG-CANCER,ADOPTIVE IMMUNOTHERAPY,ANTIGENIC PEPTIDES,ADVERSE EVENT,SINGLE-CHAIN},
  language     = {eng},
  pages        = {14},
  title        = {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},
  year         = {2012},
}

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