Reference - Detail
|Author||Wang B, Iriguchi S, Waseda M, Ueda N, Ueda T, Xu H, Minagawa A, Ishikawa A, Yano H, Ishi T, Ito R, Goto M, Takahashi R, Uemura Y, Hotta A, Kaneko S.|
|Title||Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells.|
|Journal||Nat Biomed Eng|
Avoiding the immune rejection of transplanted T cells is central to the success of allogeneic cancer immunotherapies. One solution to protecting T-cell grafts from immune rejection involves the deletion of allogeneic factors and of factors that activate cytotoxic immune cells. Here we report the generation of hypoimmunogenic cancer-antigen-specific T cells derived from induced pluripotent stem cells (iPSCs) lacking β2-microglobulin, the class-II major histocompatibility complex (MHC) transactivator and the natural killer (NK) cell-ligand poliovirus receptor CD155, and expressing single-chain MHC class-I antigen E. In mouse models of CD20-expressing leukaemia or lymphoma, differentiated T cells expressing a CD20 chimeric antigen receptor largely escaped recognition by NKG2A+ and DNAM-1+ NK cells and by CD8 and CD4 T cells in the allogeneic recipients while maintaining anti-tumour potency. Hypoimmunogenic iPSC-derived T cells may contribute to the creation of off-the-shelf T cell immunotherapies.
|MeSH||Animals Antigens, Differentiation, T-Lymphocyte / metabolism Cell Differentiation Cell Line Gene Knockout Techniques Genetic Engineering Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / immunology Leukemia / immunology Leukemia / therapy* Lymphoma / immunology Lymphoma / therapy* Male Mice NK Cell Lectin-Like Receptor Subfamily C / metabolism Receptors, Virus / genetics* T-Lymphocytes / cytology T-Lymphocytes / immunology T-Lymphocytes / transplantation* Xenograft Model Antitumor Assays beta 2-Microglobulin / genetics*|
|Human and Animal Cells||HEV0060|