A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy

A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy

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Left Foot Pad The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine.However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation.To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs.Activation of iC9 with a specific chemical inducer of dimerization (CID) initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs.We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL) therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killing activity.

iC9-expressing rejCTLs exert antitumor effects in vivo.The system efficiently and safely induces apoptosis in these Tote Bag rejCTLs.These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy.