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An Efficient Single-Cell RNA-Seq Approach to Identify Neoantigen-Specific T Cell Receptors

Lu, Yong-Chen et al.

Molecular therapy. Volume 26:Number 2 (2018, February 7th); pp 379-389 -- Cell Press

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  • Title:
    An Efficient Single-Cell RNA-Seq Approach to Identify Neoantigen-Specific T Cell Receptors
  • Author: Lu, Yong-Chen;
    Zheng, Zhili;
    Robbins, Paul F.;
    Tran, Eric;
    Prickett, Todd D.;
    Gartner, Jared J.;
    Li, Yong F.;
    Ray, Satyajit;
    Franco, Zulmarie;
    Bliskovsky, Valery;
    Fitzgerald, Peter C.;
    Rosenberg, Steven A.
  • Found In: Molecular therapy. Volume 26:Number 2 (2018, February 7th); pp 379-389
  • Journal Title: Molecular therapy
  • Subjects: Gene therapy--Periodicals; Molecular genetics--Periodicals; cancer immunotherapy--single cell--gene therapy; Dewey: 615.89505
  • Rights: Licensed
  • Publication Details: Cell Press
  • Abstract: The adoptive transfer of neoantigen-reactive tumor-infiltrating lymphocytes (TILs) can result in tumor regression in patients with metastatic cancer. To improve the efficacy of adoptive T cell therapy targeting these tumor-specific mutations, we have proposed a new therapeutic strategy, which involves the genetic modification of autologous T cells with neoantigen-specific T cell receptors (TCRs) and the transfer of these modified T cells back to cancer patients. However, the current techniques to isolate neoantigen-specific TCRs are labor intensive, time consuming, and technically challenging, not suitable for clinical applications. To facilitate this process, a new approach was developed, which included the co-culture of TILs with tandem minigene (TMG)-transfected or peptide-pulsed autologous antigen-presenting cells (APCs) and the single-cell RNA sequencing (RNA-seq) analysis of T cells to identify paired TCR sequences associated with cells expressing high levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2). Following this new approach, multiple TCRs were identified, synthesized, cloned into a retroviral vector, and then transduced into donor T cells. These transduced T cells were shown to specifically recognize the neoantigens presented by autologous APCs. In conclusion, this approach provides an efficient procedure to isolate neoantigen-specific TCRs for clinical applications, as well as for basic and translational research. The identification of antigen-specific T cell receptors (TCRs) is a complicated process, which is technically challenging and not suitable for clinical applications. To simplify this process, Lu and colleagues developed an efficient single-cell approach, which can significantly reduce the labor and time for the TCR isolation.
  • Identifier: System Number: ETOCvdc_100085636899.0x000001; Journal ISSN: 1525-0016; 10.1016/j.ymthe.2017.10.018
  • Publication Date: 2018
  • Physical Description: Electronic
  • Shelfmark(s): 5900.856500
  • UIN: ETOCvdc_100085636899.0x000001

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