Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo
Miki Ando,
Jun Ando,
Satoshi Yamazaki,
Midori Ishii,
Yumi Sakiyama,
Sakiko Harada,
Tadahiro Honda,
Tomoyuki Yamaguchi,
Masanori Nojima,
Koichi Ohshima,
Hiromitsu Nakauchi,
Norio Komatsu
Affiliations
Miki Ando
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan;Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Jun Ando
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
Satoshi Yamazaki
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Midori Ishii
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
Yumi Sakiyama
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Sakiko Harada
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
Tadahiro Honda
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
Tomoyuki Yamaguchi
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Masanori Nojima
Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Koichi Ohshima
Department of Pathology, School of Medicine, Kurume University, Fukuoka, Japan
Hiromitsu Nakauchi
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
Norio Komatsu
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
Functionally rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes (CTL) are expected to be a potent immunotherapy for tumors. When L-asparaginase-containing standard chemotherapy fails in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), no effective salvage therapy exists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of ENKL in vivo by Epstein-Barr virus-specific iPSC-derived antigen-specific CTL, with iPSC-derived antigen-specific CTL persisting as central memory T cells in the mouse spleen for at least six months. The anti-tumor response is so strong that any concomitant effect of the programmed cell death 1 (PD-1) blockade is unclear. These results suggest that long-term persistent Epstein-Barr virus-specific iPSC-derived antigen-specific CTL contribute to a continuous anti-tumor effect and offer an effective salvage therapy for relapsed and refractory ENKL.
