[iPSC-derived next-generation T cell therapy for refractory malignancies].

Abstract

My research group developed cytotoxic T lymphocytes (CTLs) redifferentiated from iPS cells (iPSC) established from antigen-specific CTLs that are rejuvenated, exhibiting a younger memory T cell phenotype with robust tumor-killing activity, and can be produced in unlimited quantities. We later introduced a chimeric antigen receptor (CAR) into these iPSC-derived rejuvenated CTLs (rejTs) to mitigate tumor antigen escape. These dual-antigen receptor rejTs can recognize both CD19 via CAR and MHC class I-presented LMP2 antigen via endogenous T cell receptors, and show a synergistic antitumor effect against EBV-associated lymphomas and longer persistence in vivo. We also generated HLA class I-edited virus-specific rejTs using CRISPR/Cas9 genome editing technology. These rejTs not only minimize recipient immune rejection, but also retain more robust cytotoxicity against virus-associated tumors compared to the original CTLs. We believe that these next-generation T cells offer a sustainable and promising approach to "off-the-shelf" T cell therapy.