The therapeutic potential of multiclonal tumoricidal T cells derived from tumor infiltrating lymphocyte-derived iPS cells

Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice. The optimization of TIL preparation has been investigated to reduce the senescence and increase the abundance of TIL, as both the q...

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Bibliographic Details
Published in:Communications biology 2021-06, Vol.4 (1), Article 694
Main Authors: Ito, Takeshi, Kawai, Yohei, Yasui, Yutaka, Iriguchi, Shoichi, Minagawa, Atsutaka, Ishii, Tomoko, Miyoshi, Hiroyuki, Taketo, M. Mark, Kawada, Kenji, Obama, Kazutaka, Sakai, Yoshiharu, Kaneko, Shin
Format: Article
Language:English
Subjects:
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Biology
Biomedical and Life Sciences
Cancer
Cell differentiation
Colorectal cancer
Colorectal carcinoma
Life Sciences
Lymphocytes
Lymphocytes T
Senescence
Tumor-infiltrating lymphocytes
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Summary:Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice. The optimization of TIL preparation has been investigated to reduce the senescence and increase the abundance of TIL, as both the quality and quantity of the transferred cells have great influence on the outcome of TIL-based ACT (TIL-ACT). Considering the effects of cell reprogramming on senescence, we expected that the anti-tumor effect could be enhanced by TIL regeneration. To confirm this hypothesis, we established tumor-specific TIL-derived iPS cells (TIL-iPSC) with human colorectal cancer specimens. T cells differentiated from TIL-iPSC (TIL-iPS-T) retained not only intrinsic T cell functions and tumor specificity, but also exhibited improved proliferation capacity and additional killing activity. Moreover, less differentiated profiles and prolonged persistency were seen in TIL-iPS-T compared with primary cells. Our findings imply that iPSC technology has great potential for TIL-ACT. Ito et al. generated and characterized multiclonal tumoricidal T cells derived from tumor infiltrating lymphocyte-derived iPS cells (TIL-iPSC) using human colorectal cancer specimens. They demonstrated that the newly-generated T cells retained intrinsic characters and acquired improved functions with less differentiated profiles, thus constituting a potential therapeutic anti-cancer tool.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-021-02195-x