Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients

Abstract

Author contributions T.D. and S.S. designed the experiments, supervised the project, and wrote the manuscript. X.H. performed the adaptive and innate immunobiology experiments, molecular biology and imaging studies and cell culture work and analyzed the data. A.G. performed imaging studies and analyzed the data. D.W. performed the in vivo and immunofluorescence imaging studies (confocal microscopy) and histopathology. G.T. performed imaging studies and cell injections. C.D. and W.O.T. generated BLT mice and performed the BLT imaging experiments. A.W. and J.V.G. designed and supervised the experiments using BLT mice. W.O.T. and C.D. performed the experiments using BLT mice. H.R., M.M.D. and L.L.L. gave technical support and conceptual advice. All authors contributed to editing the manuscript.

Induced Pluripotent Stem Cell-derived CAR-Macrophage Cells with Antigen-dependent Anti-Cancer Cell Functions for Liquid and Solid Tumors

“…Second, increasingly complicated genome engineering approaches can be applied to iPSCs, followed by single clone expansion and thorough characterization to obtain a clonal and genetically homogenous population with minimal off-target risk. Third, the seed iPSC clone can be expanded in large scale, and when combined with the recently reported techniques in making immune-tolerant universal iPSCs [25][26][27] , CAR-iMac can be developed into an off-the-shelf product with unlimited sources. The last two points are particularly useful when the effector cells from primary cell sources are difficult to engineer and to expand which is the case for PBMC-derived macrophage cells.…”

Genetically Modified Humans: The X-Men of Scientific Research

“…First demonstrated by transplanting mouse iPSCs into mismatched, healthy mice and then again by transplanting human iPSCs into humanized mice, the researchers found that the cells did not elicit any form of immune response and were able to evade the radar of the immune system [4]. …”

Re‐entering the pluripotent state from blood lineage: promises and pitfalls of blood reprogramming

“…T lymphocytes attack malignant and virus-infected cells with the help of antigen-specific TCR [47]. More recently, iPSCs with enhanced immune-evading capacity have been established [49,50]. To generate abundant 'young' T cells, Nishimura et al have reported the derivation of iPSCs from CD8 + T cells collected from the peripheral blood of an HIV patient [17].…”

“…Since genetically modified B cells have been developed to generate anti-HIV-1 neutralizing antibodies (bNAbs) [48], clinically potent monoclonal B cells derived from iPSCs are considered to be a viable source of such antibodies. More recently, iPSCs with enhanced immune-evading capacity have been established [49,50]. Engineered iPSCs are shown to circumvent both immune T and NK cells when knocked out of human leucocyte antigens (HLAs) A and B via CRISPR, while retaining one allele of HLA-C [50].…”