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In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
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Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional

Soyoko Morimoto1, Fumihiro Fujiki2, Kenta Kondo3

  • 1Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.

Oncotarget
|October 23, 2018
PubMed

Insights

A new 2D3 cell line precisely evaluates T cell receptor (TCR) functional avidity for adoptive T-cell therapy. This tool aids in developing cancer immunotherapies by assessing TCR effectiveness against tumor antigens.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Adoptive T-cell therapy using T cell receptor (TCR)-engineered T cells is a promising cancer treatment.
  • Therapeutic success hinges on the functional avidity of engineered TCRs against tumor antigens.
  • A need exists for efficient and precise methods to evaluate TCR functional avidity.

Purpose of the Study:

  • To introduce a novel platform cell line, 2D3, for efficient and precise evaluation of TCR functional avidity.
  • To validate the utility of the 2D3 cell line in assessing TCRs targeting Wilms' tumor gene 1 (WT1).

Main Methods:

  • Development of the 2D3 cell line, a reporter system utilizing green fluorescent protein (GFP) expression.
  • TCR signaling activates nuclear factor of activated T cells (NFAT), driving GFP expression for avidity assessment.
  • Transduction of four HLA-A*24:02-restricted WT1-specific CD8+ cytotoxic T lymphocyte (CTL) TCRs into 2D3 cells.

Main Results:

  • The 2D3 cell line enabled efficient and precise evaluation of the functional avidity of the four transduced TCRs.
  • Evaluated TCR functional avidity showed a positive correlation with T cell proliferation, cytokine production, and WT1-specific cytotoxicity.
  • The 2D3 cell line demonstrated stability and utility in assessing TCR performance against the WT1 antigen.

Conclusions:

  • The 2D3 cell line is a novel and stable tool for evaluating the functional avidity of TCRs.
  • This platform facilitates the development of effective TCR-based immunotherapies for cancer treatment.
  • Precise functional avidity assessment is crucial for optimizing TCR-engineered T cell therapies.
Keywords:
TCRTCR functional avidityTCR-engineered T-cell therapyWT1

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