Derivation of mimetic ?? T cells endowed with cancer recognition receptors from reprogrammed ?? T cell.

ABSTRACT: Using induced pluripotent stem cells (iPSCs) to derive chimeric antigen receptor-modified T (CAR-T) cells has great industrial potential. A previous study used ?? T cell-derived CAR-modified iPSCs to produce CAR-T cells. However, these ?? T cells are restricted to autologous use and only recognize single cancer antigen. To make CAR-T alternative for allogeneic use, we reprogrammed ?? T cell into iPSCs (?? T-iPSCs) to circumvent the risk of graft-versus-host disease. To target multiple cancer-associated antigens, we used an "NK cell-promoting" protocol to differentiate ?? T-iPSCs and to induce expression of natural killer receptors (NKRs). Through such two-step strategy, mimetic ?? T cells endowed with an array of NKRs and thus designated as "?? natural killer T (?? NKT) cells" were derived. With no/low-level expression of inhibitory killer cell immunoglobulin-like receptors (KIRs) and immune checkpoint receptors, ?? NKT cells may provide a potent "off-the-shelf" cytotoxic cell source to recognize multiple ubiquitous antigens in a broad spectrum of cancers.

SUBMITTER: Zeng J 

PROVIDER: S-EPMC6508724 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature