RRC ID 72499
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
Abstract 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.
Volume 5(5)
Pages 429-440
Published 2021-5-1
DOI 10.1038/s41551-021-00730-z
PII 10.1038/s41551-021-00730-z
PMID 34002062
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*
IF 18.952
Human and Animal Cells HEV0060