In:
Clinical and Developmental Immunology, Hindawi Limited, Vol. 2012 ( 2012), p. 1-14
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 αβ 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 α 3/V β 28 and TCR-V α 38/V β 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.
Type of Medium:
Online Resource
ISSN:
1740-2522
,
1740-2530
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2012
detail.hit.zdb_id:
2817541-4
detail.hit.zdb_id:
2119272-8
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