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

• Published in: PloS one Vol. 14; no. 5; p. e0216815
• Main Authors: Zeng, Jieming, Tang, Shin Yi, Wang, Shu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2019; Public Library of Science (PLoS)
• Subjects: Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Autografts; Bioengineering; Biology and Life Sciences; Cancer; Chimeric antigen receptors; Clinical trials; Cytotoxicity; Genetic engineering; Genomes; Graft-versus-host reaction; HCT116 Cells; Health risks; Hep G2 Cells; Humans; Immune checkpoint; Immune system; Immunoglobulin-like receptors; Immunology; Induced Pluripotent Stem Cells - immunology; Induced Pluripotent Stem Cells - pathology; Inhibitory postsynaptic potentials; K562 Cells; Killer cell immunoglobulin-like receptors; Leukemia; Ligands; Lymphocytes; Lymphocytes T; MCF-7 Cells; Medical research; Medicine; Medicine and Health Sciences; Nanotechnology; Natural killer cells; Natural Killer T-Cells - immunology; Natural Killer T-Cells - pathology; Neoplasms - genetics; Neoplasms - immunology; Pluripotency; Receptors; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Chimeric Antigen - genetics; Receptors, Chimeric Antigen - immunology; Stem cells; T cell receptors; THP-1 Cells; England; Singapore
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216815

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