1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
14
Themeli, M., Rivière, I. & Sadelain, M. New cell sources for T cell engineering
and adoptive immunotherapy. Cell Stem Cell 16, 357–366 (2015).
Timmermans, F. et al. Generation of T cells from human embryonic stem cellderived hematopoietic zones. J. Immunol. 182, 6879–6888 (2009).
Kennedy, M. et al. T lymphocyte potential marks the emergence of definitive
hematopoietic progenitors in human pluripotent stem cell differentiation
cultures. CellReports 2, 1722–1735 (2012).
Nishimura, T. et al. Generation of rejuvenated antigen-specific T cells by
reprogramming to pluripotency and redifferentiation. Cell Stem Cell 12,
114–126 (2013).
Wakao, H. et al. Expansion of functional human mucosal-associated invariant
T cells via reprogramming to pluripotency and redifferentiation. Cell Stem Cell
12, 546–558 (2013).
Vizcardo, R. et al. Regeneration of human tumor antigen-specific T cells from
iPSCs derived from mature CD8(+) T cells. Cell Stem Cell 12, 31–36 (2013).
Themeli, M. et al. Generation of tumor-targeted human T lymphocytes from
induced pluripotent stem cells for cancer therapy. Nat. Biotechnol. 31,
928–933 (2013).
Maeda, T. et al. Regeneration of CD8αβ T Cells from T-cell-Derived iPSC
Imparts Potent Tumor Antigen-Specific Cytotoxicity. Cancer Res. 76,
6839–6850 (2016).
Minagawa, A. et al. Enhancing T cell receptor stability in rejuvenated iPSCderived T cells improves their use in cancer immunotherapy. Cell Stem Cell 23,
850–858e4 (2018).
Ditadi, A., Sturgeon, C. M. & Keller, G. A view of human haematopoietic
development from the petri dish. Nat. Rev. Mol. Cell Biol. 18, 56–67 (2017).
Ivanovs, A. et al. Human haematopoietic stem cell development: from the
embryo to the dish. Development 144, 2323–2337 (2017).
Spits, H. Development of αβ T cells in the human thymus. Nat. Rev. Immunol.
2, 760–772 (2002).
La Motte-Mohs, R. N., Herer, E. & Zúñiga-Pflücker, J. C. Induction of T-cell
development from human cord blood hematopoietic stem cells by delta-like 1
in vitro. Blood 105, 1431–1439 (2005).
Awong, G. et al. Characterization in vitro and engraftment potential in vivo of
human progenitor T cells generated from hematopoietic stem cells. Blood 114,
972–982 (2009).
Petrie, H. T. & Zúñiga-Pflücker, J. C. Zoned out: functional mapping of
stromal signaling microenvironments in the thymus. Annu. Rev. Immunol. 25,
649–679 (2007).
Montel-Hagen, A. et al. Organoid-induced differentiation of conventional T cells
from human pluripotent stem cells. Cell Stem Cell 24, 376–389.e8 (2019).
17. Sturgeon, C. M., Ditadi, A., Clarke, R. L. & Keller, G. Defining the path to
hematopoietic stem cells. Nat. Biotechnol. 31, 416–418 (2013).
18. Ng, E. S. et al. Differentiation of human embryonic stem cells to HOXA+
hemogenic vasculature that resembles the aorta-gonad-mesonephros. Nat.
Biotechnol. 34, 1168–1179 (2016).
19. Nakagawa, M. et al. A novel efficient feeder-free culture system for the
derivation of human induced pluripotent stem cells. Sci. Rep. 4, 3594 (2014).
20. Vodyanik, M. A., Thomson, J. A. & Slukvin, I. I. Leukosialin (CD43) defines
hematopoietic progenitors in human embryonic stem cell differentiation
cultures. Blood 108, 2095–2105 (2006).
21. Reimann, C. et al. Human T-lymphoid progenitors generated in a feeder-cellfree delta-like-4 culture system promote T-cell reconstitution in NOD/SCID/
γc−/− mice. Stem Cells 30, 1771–1780 (2012).
22. Huijskens, M. J. A. J. et al. Technical advance: ascorbic acid induces
development of double-positive T cells from human hematopoietic stem cells
in the absence of stromal cells. J. Leukoc. Biol. 96, 1165–1175 (2014).
23. Okita, K. et al. A more efficient method to generate integration-free human
iPS cells. Nat. Methods 8, 409–412 (2011).
24. Nakatsuji, N., Nakajima, F. & Tokunaga, K. HLA-haplotype banking and iPS
cells. Nat. Biotechnol. 26, 739–740 (2008).
25. Taylor, C. J., Peacock, S., Chaudhry, A. N., Bradley, J. A. & Bolton, E. M.
Generating an iPSC bank for HLA-matched tissue transplantation based on
known donor and recipient HLA types. Cell Stem Cell 11, 147–152 (2012).
26. Ohminami, H., Yasukawa, M. & Fujita, S. HLA class I-restricted lysis of
leukemia cells by a CD8(+) cytotoxic T-lymphocyte clone specific for WT1
peptide. Blood 95, 286–293 (2000).
27. Ochi, T. et al. Novel adoptive T-cell immunotherapy using a WT1-specific
TCR vector encoding silencers for endogenous TCRs shows marked
antileukemia reactivity and safety. Blood 118, 1495–1503 (2011).
28. Sato, T., Tachibana, K., Nojima, Y., D’Avirro, N. & Morimoto, C. Role of the
VLA-4 molecule in T cell costimulation. Identification of the tyrosine
phosphorylation pattern induced by the ligation of VLA-4. J. Immunol. 155,
2938–2947 (1995).
29. Ishikawa, T. et al. Phase I clinical trial of fibronectin CH296-stimulated T cell
therapy in patients with advanced cancer. PLoS ONE 9, e83786 (2014).
30. Yu, S. S. et al. In vivo persistence of genetically modified T cells generated
ex vivo using the fibronectin CH296 stimulation method. Cancer Gene Ther.
15, 508–516 (2008).
31. Hurton, L. V. et al. Tethered IL-15 augments antitumor activity and promotes
a stem-cell memory subset in tumor-specific T cells. Proc. Natl Acad. Sci. USA
113, E7788–E7797 (2016).
32. Uenishi, G. et al. Tenascin C promotes hematoendothelial development and T
lymphoid commitment from human pluripotent stem cells in chemically
defined conditions. Stem Cell Rep. 3, 1073–1084 (2014).
33. Kitayama, S. et al. Cellular adjuvant properties, direct cytotoxicity of redifferentiated Vα24 invariant NKT-like cells from human induced pluripotent
stem cells. Stem Cell Rep. 6, 213–227 (2016).
34. Ueda, N. et al. Generation of TCR-expressing innate lymphoid-like helper
cells that induce cytotoxic T cell-mediated anti-leukemic cell response. Stem
Cell Rep. 10, 1935–1946 (2018).
35. Brauer, P. M., Singh, J., Xhiku, S. & Zúñiga-Pflücker, J. C. T cell genesis:
in vitro veritas est? Trends Immunol. 37, 889–901 (2016).
36. Wakabayashi, Y. et al. Bcl11b is required for differentiation and survival of
alphabeta T lymphocytes. Nat. Immunol. 4, 533–539 (2003).
37. Janas, M. L. et al. Thymic development beyond beta-selection requires
phosphatidylinositol 3-kinase activation by CXCR4. J. Exp. Med. 207, 247–261
(2010).
38. Trampont, P. C. et al. CXCR4 acts as a costimulator during thymic betaselection. Nat. Immunol. 11, 162–170 (2010).
39. Calderón, L. & Boehm, T. Synergistic, context-dependent, and hierarchical
functions of epithelial components in thymic microenvironments. Cell 149,
159–172 (2012).
40. Sommermeyer, D. et al. Chimeric antigen receptor-modified T cells derived
from defined CD8+ and CD4+ subsets confer superior antitumor reactivity
in vivo. Leukemia 30, 492–500 (2016).
41. Xu, H. et al. Targeted disruption of HLA genes via CRISPR-Cas9 generates
iPSCs with enhanced immune compatibility. Cell Stem Cell 24, 566–578.e7
(2019).
42. Deuse, T. et al. Hypoimmunogenic derivatives of induced pluripotent stem
cells evade immune rejection in fully immunocompetent allogeneic recipients.
Nat. Biotechnol. 37, 252–258 (2019).
43. Gornalusse, G. G. et al. HLA-E-expressing pluripotent stem cells escape
allogeneic responses and lysis by NK cells. Nat. Biotechnol. 35, 765–772
(2017).
44. Iriguchi, S. et al. Feeder-free differentiation and expansion for T cells from
induced pluripotent stem cells. Protoc. Exch. (2020).
45. Kitamura, T. et al. Retrovirus-mediated gene transfer and expression cloning:
powerful tools in functional genomics. Exp. Hematol. 31, 1007–1014 (2003).
NATURE COMMUNICATIONS | (2021)12:430 | https://doi.org/10.1038/s41467-020-20658-3 | www.nature.com/naturecommunications
A Self-archived copy in
Kyoto University Research Information Repository
https://repository.kulib.kyoto-u.ac.jp
NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-20658-3
46. Cosset, F. L., Takeuchi, Y., Battini, J. L., Weiss, R. A. & Collins, M. K. Hightiter packaging cells producing recombinant retroviruses resistant to human
serum. J. Virol. 69, 7430–7436 (1995).
ARTICLE
from Takeda Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sumitomo Chemical Co., Ltd., and Thyas Co., Ltd. S.A., M.K., T. Sato., Y.B., T.S., K.N., M.T., Y. Kassai,
and A.H. are employees of Takeda Pharmaceutical Co. Ltd. Y.Y. is an employee of Thyas
Co. Ltd. The remaining authors declare no competing financial interests. These authors
and all other authors declare no other competing interests.
Acknowledgements
We thank Prof. Shinya Yamanaka (Kyoto University) for providing the HLA homozygous
iPSC line and giving critical advice for our research work. We also thank Prof. Hiromitsu
Nakauchi (The University of Tokyo) and Prof. Naoko Takasu (Kyoto University) for
providing the iPSC lines; Dr. Seigo Izumo (T-CiRA) for giving critical advice; Dr. Wang
Bo (Kyoto University); Dr. Keiko Koga, Dr. Masashi Yamada, and Dr. Sujatha Mohan (TCiRA); Mr. Shuichi Kitayama, Mr. Kohei Ohara, and Mr. Akito Tanaka (Kyoto University); Ms. Ayako Kumagai, Sanae Kamibayashi, Ms. Eri Imai, and Ms. Katsura Noda
(Kyoto University); Ms. Mariko Sekiguchi, Ms. Maki Numazaki, Ms. Yuka Maruyama,
Ms. Yuki Watanabe, Ms. Ai Kikuchi, Ms. Xuewei Song, Ms. Hitomi Takakubo, Ms.
Megumi Tada, and Ms. Mizuki Kobayashi (T-CiRA) for technical and administrative
assistances. The entire study was conducted in accordance with the Declaration of Helsinki and permitted by the institutional ethical board of Kyoto University. This work was
supported in part by the Ministry of Education, Culture, Sports, Science and Technology
of Japan (23591413, 15H04655, 15J05263, 26293357, and 18K16085), Japan Agency for
Medical Research and Development (Project for Development of Innovative Research on
Cancer Therapeutics, and Core Center for iPS Cell Research), the Takeda-CiRA collaboration program, and the collaborative research grant of Thyas Co., Ltd.
Author contributions
S.I., Y.Y., Y.K., and S.K. designed the study; S.I., Y.Y., Y.K., and S.K. interpreted the data;
S.I., Y.Y., Y.K., S.A., M.K., T.Sato., T.U., N.Y., Y.M., Y.B., M.Y., and Y.Kassai performed
the experiments; S.I., S.A., M.K., A.H., and S.K. analyzed the data; Y. Mishima, A.M., T.S.,
K.N., M.T., T.N., and M.Y. provided critical materials, protocols or advice for the
experiments; S.K. supervised the study; and S.I. and S.K. wrote the manuscript.
Competing interests
The authors declare the following financial competing interests. S.K. is a founder,
shareholder, and chief scientific officer at Thyas Co., Ltd. and received research fundings
Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41467020-20658-3.
Correspondence and requests for materials should be addressed to S.K.
Peer review information Nature Communications thanks the anonymous reviewer(s) for
their contribution to the peer review of this work. Peer reviewer reports are available.
Reprints and permission information is available at http://www.nature.com/reprints
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2021
NATURE COMMUNICATIONS | (2021)12:430 | https://doi.org/10.1038/s41467-020-20658-3 | www.nature.com/naturecommunications
15
...
論文の公開元へ
