Sustainable tumor suppressive effect of iPSC-derived rejuvenated T cells targeting cervical cancers

Abstract Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTL) can survive long-term as young memory T cells in vivo, with continuous tumor eradication. Banking of iPSCs as an unlimited “off-the-shelf” source of therapeutic T cells may be feasible. To generate safer iPSC, we reprogrammed human papilloma virus type16 (HPV16) E6-specific CTL by Sendai virus vector without cotransduction of SV40 large T antigen. The iPSC efficiently differentiated into HPV16-specific rejuvenated CTL that demonstrated robust cytotoxicity against cervical cancer. The tumor suppressive effect of rejuvenated CTL was stronger and more persistent than that of original peripheral blood CTL. These rejuvenated HPV16-specific CTL provide a sustained tumor suppressive effect even for epithelial cancers and constitute promising immunotherapy for cervical cancer.