Cloning and expansion of antigen-specific T cells using iPS cell technology: development of "off-the-shelf" T cells for the use in allogeneic transfusion settings.

Int J Hematol

Laboratory of Immunology, Institute for Frontier Life and Medical Science, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Published: March 2018

AI Article Synopsis

  • Recent advances in adoptive immunotherapy have shown moderate success but face challenges with the exhaustion of cytotoxic T lymphocytes (CTLs) during culture.
  • A new strategy using induced pluripotent stem cell (iPSC) technology aims to regenerate CTLs that maintain their original antigen specificity.
  • The research includes developing a method to create "off-the-shelf" T cells by introducing T cell receptor genes into non-T derived iPSCs, with an initial trial planned for relapsed acute myeloid leukemia patients targeting the WT1 antigen.

Article Abstract

Recent advances in adoptive immunotherapy using cytotoxic T lymphocytes (CTLs) have led to moderate therapeutic anti-cancer effects in clinical trials. However, a critical issue, namely that CTLs collected from patients are easily exhausted during expansion culture, has yet to be solved. To address this issue, we have been developing a strategy which utilizes induced pluripotent stem cell (iPSC) technology. This strategy is based on the idea that when iPSCs are produced from antigen-specific CTLs, CTLs regenerated from such iPSCs should show the same antigen specificity as the original CTLs. Pursuing this idea, we previously succeeded in regenerating melanoma antigen MART1-specific CTLs, and more recently in producing potent CTLs expressing CD8αβ heterodimer. We are now developing a novel method by which non-T derived iPSCs are transduced with exogenous T cell receptor genes. If this method is applied to Human Leukocyte Antigen (HLA) haplotype-homozygous iPSC stock, it will be possible to prepare "off-the-shelf" T cells. As a first-in-human trial, we are planning to apply our strategy to relapsed acute myeloid leukemia patients by targeting the WT1 antigen.

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Source
http://dx.doi.org/10.1007/s12185-018-2399-1DOI Listing

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