'Off-the-shelf' immunotherapy with iPSC-derived rejuvenated cytotoxic T lymphocytes

Abstract

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.