'Off-the-shelf' immunotherapy with iPSC-derived rejuvenated cytotoxic T lymphocytes.
Adoptive T-cell therapy to target and kill tumor cells shows promise and induces durable remissions in selected malignancies. However, for most cancers, clinical utility is limited. Cytotoxic T lymphocytes continuously exposed to viral or tumor antigens, with long-term expansion, may become unable to proliferate ("exhausted"). To exploit fully rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes is a potentially powerful approach. We review recent progress in engineering iPSC-derived T cells and prospects for clinical translation. We also describe the importance of introducing a suicide gene safeguard system into adoptive T-cell therapy, including iPSC-derived T-cell therapy, to protect from unexpected events in first-in-humans clinical trials.
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: mando@ims.u-tokyo.ac.jp.
Miki
M
Ando
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Hiromitsu
H
Nakauchi
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D060846:Cell Engineering; D064987:Cell- and Tissue-Based Therapy; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell