International Journal of Hematology

DOI: 10.1007/s12185-018-2399-1 Pages: 271-277

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

1. Kyoto University, Laboratory of Immunology, Institute for Frontier Life and Medical Science

2. Kyoto University, Department of Hematology and Oncology, Graduate School of Medicine

3. National Cancer Institute, Center for Cancer Research

Correspondence to:
Hiroshi Kawamoto
Tel: (81)-75-751-3815
Email: kawamoto@infront.kyoto-u.ac.jp

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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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