title: Efficient Regeneration of Human Vα24+Invariant Natural Killer T Cells and Their Anti-Tumor Activity In Vivo.
abstract: Reprogramming of antigen-specific T lymphocytes into induced pluripotent stem cells (iPSCs) and their subsequent re-differentiation has enabled expansion of functional T lymphocytes in vitro, thus opening up new approaches for immunotherapy of cancer and other diseases. In this study, we have established a robust protocol to reprogram human invariant NKT (Vα24+iNKT) cells, which have been shown to act as cellular adjuvants and thus exert anti-tumor activity in mice and humans, and to re-differentiate the iNKT cell-derived iPSCs into functional iNKT cells. These iPSC-derived iNKT cells (iPS-Vα24+iNKT cells) can be activated by ligand-pulsed dendritic cells (DCs) and produce a large amount of interferon-γ upon activation, as much as parental Vα24+iNKT cells, but exhibit even better cytotoxic activity against various tumor cell lines. The iPS-Vα24+iNKT cells possess significant anti-tumor activity in tumor-bearing mice and can activate autologous NK cells upon activation by ligand-pulsed DCs in the NOG mouse model in vivo, further extending their therapeutic potential. This study thus provides a first proof of concept for the clinical application of human iPS-Vα24+iNKT cells for cancer immunotherapy. Stem Cells 2016;34:2852-2860.
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science (IMS).
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Raul
authors.initials: R
authors.lastname: Vizcardo
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science (IMS).
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science (IMS).
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Genta
authors.initials: G
authors.lastname: Kitahara
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Okoshi
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science (IMS).
authors.forename: Maki
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Laboratory for Immunoregulation, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science (IMS), Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science (IMS).
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Fujii
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012038:Regeneration
chemical_list: D000970:Antineoplastic Agents; D011948:Receptors, Antigen, T-Cell; C528689:Valpha24 protein, human
keywords: Immunotherapy; Induced pluripotent stem cells; Invariant NKT cells; NK cells; Reprogramming