Long-term eradication of extranodal NK/T cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo

Functionally rejuvenated induced pluripotent stem cell-derived antigen-specific cytotoxic T lymphocytes are expected to be potent immunotherapy for tumors. When L- asparaginase-containing standard chemotherapy fails in extranodal NK/T cell lymphoma, nasal type, no effective salvage therapyexists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of extranodal NK/T cell lymphoma, nasal type, in vivo by Epstein-Barr virus-specific induced pluripotent stem cell-derived antigen-specific cytotoxic T lymphocytes, with induced pluripotent stem cell-derived antigen-specific cytotoxic T lymphocytes persisting as central memory T cellsin mouse spleen for at least 6 months. The anti-tumor response is so strong that any concomitant effect of PD-1 blockade is unclear. These results suggest that long-term persistent Epstein-Barr virus-specific induced pluripotent stem cell-derived antigen-specific cytotoxic T lymphocytes contribute to continuous anti-tumor effect and offer an effective salvage therapyfor relapsed and refractory extranodal NK/T cell lymphoma, nasal type.