RRC ID 63627
Author Iriguchi S, Yasui Y, Kawai Y, Arima S, Kunitomo M, Sato T, Ueda T, Minagawa A, Mishima Y, Yanagawa N, Baba Y, Miyake Y, Nakayama K, Takiguchi M, Shinohara T, Nakatsura T, Yasukawa M, Kassai Y, Hayashi A, Kaneko S.
Title A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy.
Journal Nat Commun
Abstract Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of "off-the-shelf" T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce "off-the-shelf" and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology.
Volume 12(1)
Pages 430
Published 2021-1-18
DOI 10.1038/s41467-020-20658-3
PII 10.1038/s41467-020-20658-3
PMID 33462228
PMC PMC7814014
MeSH Animals Cell Culture Techniques / methods* Cell Differentiation / drug effects Cell Line, Tumor Chemokine CXCL12 / metabolism Culture Media / metabolism Culture Media / pharmacology Female Humans Imidazoles / pharmacology Immunotherapy, Adoptive / methods* Induced Pluripotent Stem Cells / physiology* Mice Neoplasms / immunology Neoplasms / therapy* Pyridines / pharmacology Receptors, Chimeric Antigen / immunology T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Cytotoxic / transplantation* Xenograft Model Antitumor Assays
IF 12.121
Human and Animal Cells NALM-6(RCB1933) CCRF-CEM(RCB1980)