SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma

Choe JH, Watchmaker PB, Simic MS, Gilbert RD, Li AW, Krasnow NA, Downey KM, Yu W, Carrera DA, Celli A, Cho J, Briones JD, Duecker JM, Goretsky YE, Dannenfelser R, Cardarelli L, Troyanskaya O, Sidhu SS, Roybal KT, Okada H, Lim WA.
Sci Transl Med. 2021 Apr 28;13(591):eabe7378. doi: 10.1126/scitranslmed.abe7378. PMID:33910979

Of Interest Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells Hypothesis: Induction of Autoimmunity in Type 1 Diabetes-A Lipid Focus Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes IL18 signaling causes islet β cell development and insulin secretion via different receptors on acinar and β cells Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation Deep Visual Proteomics defines single-cell identity and heterogeneity Modular design of synthetic receptors for programmed gene regulation in cell therapies Development of a scalable method to isolate subsets of stem cell-derived pancreatic islet cells Genetic manipulation of stress pathways can protect stem-cell-derived islets from apoptosis in vitro Abnormal exocrine-endocrine cell cross-talk promotes β-cell dysfunction and loss in MODY8 New insights into β-cell failure, regeneration and replacement Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation Using the T Cell Receptor as a Biomarker in Type 1 Diabetes Pancreatic islets in bed with microvasculature-companions for life Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium α-cell Gq signaling is critical for maintaining euglycemia A human ESC line for efficient CRISPR editing of pluripotent stem cells The physiological role of β-cell heterogeneity in pancreatic islet function Mutations and variants of ONECUT1 in diabetes Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells Chromogranin A Deficiency Confers Protection from Autoimmune Diabetes Via Multiple Mechanisms Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes SARS-CoV-2 infection of islet β cells: Evidence and implications Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection Engineering islets from stem cells for advanced therapies of diabetes Generation of insulin-producing pancreatic β cells from multiple human stem cell lines Defining a cure for type 1 diabetes: a call to action Breaking and restoring immune tolerance to pancreatic beta-cells in type 1 diabetes Immunotherapy: Building a bridge to a cure for type 1 diabetes Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes A human mutation in STAT3 promotes type 1 diabetes through a defect in CD8+ T cell tolerance A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR Islet-Resident Dendritic Cells and Macrophages in Type 1 Diabetes: In Search of Bigfoot’s Print SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma Uncovering Pathways to Personalized Therapies in Type 1 Diabetes Stem Cell-Based Clinical Trials for Diabetes Mellitus T cell circuits that sense antigen density with an ultrasensitive threshold HLA class I hyper-expression unmasks beta cells but not alpha cells to the immune system in pre-diabetes Consequences for Pancreatic β-Cell Identity and Function of Unregulated Transcript Processing T cells selectively filter oscillatory signals on the minutes timescale Comprehensive analysis of single cell ATAC-seq data with SnapATAC The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes Current and future therapies for type 1 diabetes Long Non-Coding RNAs as Key Modulators of Pancreatic β-Cell Mass and Function Pancreatic progenitor epigenome maps prioritize type 2 diabetes risk genes with roles in development
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