Journal Article

Transfer of mRNA Encoding Invariant NKT Cell Receptors Imparts Glycolipid Specific Responses to T Cells and gammadeltaT Cells

Dörrie, Jan, Iyoda, Tomonori, Sato, Yusuke, Schaft, Niels, Fujii, Shin-ichiro, Shinga, Jun, Yamasaki, Satoru, Kawamura, Masami, Shimizu, Kanako

2015

Overview

Cell-based therapies using genetically engineered lymphocytes expressing antigen-specific T cell receptors (TCRs) hold promise for the treatment of several types of cancers. Almost all studies using this modality have focused on transfer of TCR from CD8 cytotoxic T lymphocytes (CTLs). The transfer of TCR from innate lymphocytes to other lymphocytes has not been studied. In the current study, innate and adaptive lymphocytes were transfected with the human NKT cell-derived TCR[alpha] and [beta] chain mRNA (the V[alpha]24 and V[beta]11 TCR chains). When primary T cells transfected with NKT cell-derived TCR were subsequently stimulated with the NKT ligand, [alpha]-galactosylceramide ([alpha]-GalCer), they secreted IFN-[gamma] in a ligand-specific manner. Furthermore when [gamma][delta]T cells were transfected with NKT cell-derived TCR mRNA, they demonstrated enhanced proliferation, IFN-[gamma] production and antitumor effects after [alpha]-GalCer stimulation as compared to parental [gamma][delta]T cells. Importantly, NKT cell TCR-transfected [gamma][delta]T cells responded to both NKT cell and [gamma][delta]T cell ligands, rendering them bi-potential innate lymphocytes. Because NKT cell receptors are unique and universal invariant receptors in humans, the TCR chains do not yield mispaired receptors with endogenous TCR [alpha] and [beta] chains after the transfection. The transfection of NKT cell TCR has the potential to be a new approach to tumor immunotherapy in patients with various types of cancer.

• Publisher: Public Library of Science
• Subject: Genetic engineering / Genetically modified organisms / Lipids / Messenger RNA / T cells