Journal
MOLECULAR THERAPY
Volume 28, Issue 11, Pages 2394-2405Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2020.07.004
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Funding
- JSPS/KAKENHI [18K07273]
- AMED [JP19bm0404032, JP19be0404011]
- Grants for Cross-Disciplinary Collaboration, Juntendo University [29-13, 30-47]
- Grants-in-Aid for Scientific Research [18K07273] Funding Source: KAKEN
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Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTLs) 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 iPSCs, we reprogrammed human papilloma virus type 16 (HPV16) E6-specific CTLs by Sendai virus vector without cotransduction of SV40 large T antigen. The iPSCs efficiently differentiated into HPV16-specific rejuvenated CTLs that demonstrated robust cytotoxicity against cervical cancer. The tumor-suppressive effect of rejuvenated CTLs was stronger and more persistent than that of original peripheral blood CTLs. These rejuvenated HPV16-specific CTLs provide a sustained tumor-suppressive effect even for epithelial cancers and constitute promising immunotherapy for cervical cancer.
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