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Gene Engineering T Cells with T-Cell Receptor for Adoptive Therapy

Dian Kortleve1, Mandy van Brakel2, Rebecca Wijers2

  • 1Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands. d.kortleve@erasmusmc.nl.

Methods in Molecular Biology (Clifton, N.J.)
|May 27, 2022
PubMed

Insights

Selecting T-cell receptor (TCR)-engineered T cells for clinical trials requires rigorous preclinical testing. This study provides essential protocols to evaluate TCR specificity and sensitivity for effective target recognition.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biotechnology

Background:

  • Adoptive T-cell therapy using T-cell receptor (TCR)-engineered T cells shows promise for cancer treatment.
  • Preclinical evaluation of TCRs is crucial for ensuring safety and efficacy before clinical application.

Purpose of the Study:

  • To present a comprehensive set of protocols for the preclinical assessment of TCRs.
  • To facilitate the selection of optimal TCR candidates for clinical testing in adoptive T-cell therapy.

Main Methods:

  • TCR retrieval and annotation.
  • Gene transfer into T cells.
  • In vitro assessment of TCR specificity and sensitivity.
  • Evaluation of critical preclinical parameters.

Main Results:

  • Established a series of fundamental protocols for TCR preclinical evaluation.
  • Demonstrated a method for assessing target recognition specificity and sensitivity.
  • Enabled informed selection of TCRs for clinical development.

Conclusions:

  • The presented protocols are essential for the rigorous preclinical evaluation of TCRs.
  • This framework supports the advancement of TCR-engineered T-cell therapies towards clinical application.
Keywords:
Gene transferIn vitro assaysSensitivitySpecificityT-cell engineeringT-cell receptorTCR annotationTCR cloning

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