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Rinsho Ketsueki. 2018;59(7):932-938. doi: 10.11406/rinketsu.59.932.

[iPSC-derived rejuvenated T-cell therapy for Epstein-Barr virus-associated lymphomas].

[Article in Japanese]

Author information

Department of Hematology, Juntendo University School of Medicine.
Division of Stem Cell Therapy, The Institute of Medical Science, The University of Tokyo.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine.


Extranodal natural killer (NK) /T-cell lymphoma (ENKL), nasal-type, is an aggressive lymphoma that is relatively common in Asia and is resistant to anthracycline-based chemotherapy. Antigen-specific cytotoxic T-lymphocyte (CTL) therapy can induce durable remission in selected tumors, such as melanomas and virus-related tumors. ENKLs are commonly infected with the Epstein-Barr virus (EBV) ; therefore, CTL therapy can be effective for these lymphomas. However, CTLs that are continuously exposed to viral or tumor antigens usually get exhausted. Antigen-specific CTLs generated from iPSCs have a higher proliferative capacity and longer telomeres than original CTLs and are functionally rejuvenated (rejuvenated T cell, rejT). For clinical translation, the tumorigenic potential of iPSCs and the malignant transformation of differentiated iPSCs are major safety concerns. To address these issues, we introduced inducible caspase-9 (iC9) -based safeguard system into iPSCs. iC9-rejTs exert strong anti-tumor effects against EBV-infected tumors in vivo, and the iC9 suicide gene system provides a reliable safeguard for rejT therapy. We initiated a preclinical study using this novel immunotherapy for EBV-associated lymphoma. We believe that rejT therapy can be a potential safe approach as an "off-the-shelf" therapy for refractory ENKL in the future.


EBV-associated lymphoma; Extranodal NK/T-cell lymphoma; iC9 safeguard system; iPSC-derived CTL therapy; nasal-type

[Indexed for MEDLINE]

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