{"entity": "publication", "iuid": "ac91440eef4f43c0aba9f473bd0f53cf", "timestamp": "2026-09-30T03:00:47.035Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ac91440eef4f43c0aba9f473bd0f53cf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ac91440eef4f43c0aba9f473bd0f53cf"}}, "title": "Complementarity-determining region clustering may cause CAR-T cell dysfunction.", "authors": [{"family": "Sar\u00e9n", "given": "Tina", "initials": "T", "orcid": "0000-0001-5227-6779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed75a6dcbb9940e49481280af6183d69.json"}}, {"family": "Saronio", "given": "Giulia", "initials": "G"}, {"family": "Marti Torrell", "given": "Paula", "initials": "P"}, {"family": "Zhu", "given": "Xu", "initials": "X"}, {"family": "Thelander", "given": "Josefin", "initials": "J"}, {"family": "Andersson", "given": "Yasmin", "initials": "Y"}, {"family": "Hofstr\u00f6m", "given": "Camilla", "initials": "C"}, {"family": "Nestor", "given": "Marika", "initials": "M"}, {"family": "Dimberg", "given": "Anna", "initials": "A", "orcid": "0000-0003-4422-9125", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f5d91c4b8784d8081a41604bb3d78d4.json"}}, {"family": "Persson", "given": "Helena", "initials": "H"}, {"family": "Ramachandran", "given": "Mohanraj", "initials": "M", "orcid": "0000-0003-2685-0575", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd947633edf949aba9e680e63a1e178b.json"}}, {"family": "Yu", "given": "Di", "initials": "D", "orcid": "0000-0002-8636-0351", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/80a3098e7db143a5b76d27912d59852f.json"}}, {"family": "Essand", "given": "Magnus", "initials": "M", "orcid": "0000-0002-9725-0422", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2e56cdd77634c01ab6d98dea8c60430.json"}}], "type": "journal article", "published": "2023-08-10", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "4732", "issn-l": "2041-1723"}, "abstract": "Chimeric antigen receptor (CAR)-T cell therapy is rapidly advancing as cancer treatment, however, designing an optimal CAR remains challenging. A single-chain variable fragment (scFv) is generally used as CAR targeting moiety, wherein the complementarity-determining regions (CDRs) define its specificity. We report here that the CDR loops can cause CAR clustering, leading to antigen-independent tonic signalling and subsequent CAR-T cell dysfunction. We show via CARs incorporating scFvs with identical framework and varying CDR sequences that CARs may cluster on the T cell surface, which leads to antigen-independent CAR-T cell activation, characterized by increased cell size and interferon (IFN)-\u03b3 secretion. This results in CAR-T cell exhaustion, activation-induced cell death and reduced responsiveness to target-antigen-expressing tumour cells. CDR mutagenesis confirms that the CAR-clustering is mediated by CDR-loops. In summary, antigen-independent tonic signalling can be induced by CDR-mediated CAR clustering, which could not be predicted from the scFv sequences, but could be tested for by evaluating the activity of unstimulated CAR-T cells.", "doi": "10.1038/s41467-023-40303-z", "pmid": "37563127", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10415375"}, {"db": "pii", "key": "10.1038/s41467-023-40303-z"}], "notes": [], "created": "2026-09-23T08:53:43.916Z", "modified": "2026-09-23T08:53:43.982Z"}