{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293808/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293808"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"synNotch CAR-Macrophages promote persistent antitumour activity through enhanced adaptive immunity","description":"Chimeric antigen receptor-macrophage (CAR-M) possess the ability to migrate into the immunosuppressive tumour microenvironment (TME) of solid tumours and mediate phagocytosis. However, their efficacy is limited by challenges in precisely controlling tumour-specific immune activation and sustaining adaptive antitumour responses due to systemic off-target risks and inefficient antigen presentation. To overcome these limitations, we engineered an antigen prime-and-kill circuit, wherein tumour-specific synthetic Notch (syN) receptors locally induce the production of a kill antigen. This circuit enhances the precision of CAR-M while establishing self-sustaining antigen-presentation networks, amplifying tumour-specific T-cell adaptive immunity without eliciting systemic cytokine toxicity. To enable in situ CAR-M generation, we developed a macrophage-derived exosome-based delivery system to introduce syN-CAR genes into tumour-associated macrophages (TAMs), thereby generating syN-CAR-M within the TME. These engineered CAR-M actively sought and engulfed cancer cells while promoting a robust adaptive antitumour immune response in the TME in a murine tumour model. Our findings highlight that in situ induction of syN-CAR-M triggers a potent, tumour-specific adaptive immune response, offering a novel strategy for CAR-M-based immunotherapy and advancing precision cancer treatment by enhancing efficacy while minimizing systemic toxicity.","dates":{"publication":"2026/03/01"},"accession":"GSE293808","cross_references":{"GSM":["GSM8890524","GSM8890523","GSM8890522","GSM8890521","GSM8890520","GSM8890528","GSM8890527","GSM8890526","GSM8890525"],"GPL":["24247"],"GSE":["293808"],"taxon":["Mus musculus"]}}