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Synthetic transcription factors designed by domain recombination enhance CAR T cell antitumor function
Keywords genome engineering synthetic biology transcriptional regulation CAR T cells Introduction Human protein-coding genes arose primarily through the repurposing of domains from ancestral genes via addition, deletion, or shuffling, rather than through de novo sequence creation.1,2,3,4,5,6,7 This principle inspired early protein engineering efforts, where domain shuffling was used to recombine genes, first randomly and later at pre-defined crossover points for various applications,...
Clonal lineage tracing of innate immune cells in human cancer
To establish a lineage tracing method applicable to donor-matched solid tissue and blood samples and to clonally link immune cells across tissue sites, we applied mtscATAC-seq to profile five patients with early-stage non-small cell lung cancer (NSCLC) who had undergone therapeutic lobectomy, spanning adenocarcinoma (SU-L-002, SU-L-004, SU-L-005; treatment-naïve), squamous cell carcinoma (SU-L-001; post-neoadjuvant chemotherapy), and neuroendocrine (SU-L-003) histologies (Figures 1A and S1A;...
Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy - Nature Cancer
Abstract Chimeric antigen receptor (CAR) T cells can mediate durable complete responses in individuals with certain hematologic malignancies, but antigen downregulation is a common mechanism of resistance. Although the native T cell receptor can respond to very low levels of antigen, engineered CARs cannot, likely due to inefficient recruitment of downstream proximal signaling molecules.
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