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High-throughput identification of antigen-specific TCRs by TCR gene capture. | LitMetric

AI Article Synopsis

  • * A new DNA-based high-throughput strategy has been created to capture and sequence TCR genes, resulting in a comprehensive library of TCRs that react to cancer antigens.
  • * This method allows for the identification of specific TCRs in diverse T cell populations and can pinpoint tumor-reactive TCRs within tumors without prior knowledge of the target antigens, paving the way for personalized TCR gene therapy in cancer treatment.

Article Abstract

The transfer of T cell receptor (TCR) genes into patient T cells is a promising approach for the treatment of both viral infections and cancer. Although efficient methods exist to identify antibodies for the treatment of these diseases, comparable strategies to identify TCRs have been lacking. We have developed a high-throughput DNA-based strategy to identify TCR sequences by the capture and sequencing of genomic DNA fragments encoding the TCR genes. We establish the value of this approach by assembling a large library of cancer germline tumor antigen-reactive TCRs. Furthermore, by exploiting the quantitative nature of TCR gene capture, we show the feasibility of identifying antigen-specific TCRs in oligoclonal T cell populations from either human material or TCR-humanized mice. Finally, we demonstrate the ability to identify tumor-reactive TCRs within intratumoral T cell subsets without knowledge of antigen specificities, which may be the first step toward the development of autologous TCR gene therapy to target patient-specific neoantigens in human cancer.

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Source
http://dx.doi.org/10.1038/nm.3359DOI Listing

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