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

Rinsho Ketsueki. 2018;59(7):932-938. doi: 10.11406/rinketsu.59.932.
[Article in Japanese]

Abstract

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.

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

MeSH terms

  • Caspase 9 / genetics
  • Cell- and Tissue-Based Therapy
  • Epstein-Barr Virus Infections / complications*
  • Genes, Transgenic, Suicide
  • Herpesvirus 4, Human
  • Humans
  • Immunotherapy
  • Induced Pluripotent Stem Cells / cytology*
  • Lymphoma / therapy*
  • Lymphoma / virology
  • T-Lymphocytes, Cytotoxic / cytology*

Substances

  • Caspase 9