Sustainable Tumor-Suppressive Effect of iPSC-Derived Rejuvenated T Cells Targeting Cervical Cancers

Mol Ther. 2020 Nov 4;28(11):2394-2405. doi: 10.1016/j.ymthe.2020.07.004. Epub 2020 Jul 9.

Abstract

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.

Keywords: HPV-CTL; cervical cancer; human papilloma virus type 16; rejuvenated CTL; safer iPSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / immunology
  • Cytotoxicity, Immunologic*
  • Female
  • Humans
  • Immunomodulation*
  • Immunotherapy
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Oncogene Proteins, Viral / immunology
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • Repressor Proteins / immunology
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / therapy
  • Uterine Cervical Neoplasms / virology

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins