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Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers.

ABSTRACT: The clinical success of T cell receptor (TCR) gene-transduced T (TCR-T) cell therapy is expected as one of the next-generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high-functional TCRs) is important. One widely used approach to select high-functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high-functional TCRs is desired. We herein attempted to establish a simple method to select high-functional TCRs based on the expression of T cell activation markers using the mouse T cell line BW5147.3 (BW). We examined relationships between the EC50 values of TCRs in interleukin-2 production and the expression levels of TCR activation markers on BW cells. In TCR-expressing BW cells stimulated with antigenic peptides, the CD69, CD137, and PD-1 expression was differentially induced by various doses of peptides. An analysis of TCRs derived from the tumor-infiltrating lymphocytes of murine melanoma and peripheral blood T cells of hepatocellular carcinoma patients treated with a peptide vaccination revealed that an analysis combining CD69, CD137, and PD-1 expression levels in BW cells stimulated with a single dose of an antigenic peptide selected high-functional TCRs with functional avidity assessed by EC50 values. Our method facilitates the section of high-functional TCRs among tumor-reacting TCRs, which will promote TCR-T cell therapy. The stimulation of BW cells expressing objective TCRs with a single dose of antigenic peptides and analysis combining the expression of CD69, CD137, and PD-1 allows us to select highly responsive TCRs.

SUBMITTER: Thi Viet Ha M

PROVIDER: S-EPMC10236640 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers.

Thi Viet Ha My M Hamana Hiroshi H Shitaoka Kiyomi K Hayee Abdul A Kobayashi Eiji E Yoshikawa Toshiaki T Nakatsura Tetsuya T Saikawa Reiko R Sato Eri E Osawa Mitsujiro M Hitoshi Yasumichi Y Son Dang Tung T Ozawa Tatsuhiko T Kishi Hiroyuki H

Cancer science 20230328 6

The clinical success of T cell receptor (TCR) gene-transduced T (TCR-T) cell therapy is expected as one of the next-generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high-functional TCRs) is important. One widely used approach to select high-functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high-functional TCRs is desired. We herein attempte ...[more]

PMID: 36866942

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Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers.

Publications

Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers.

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