{"entity": "researcher", "timestamp": "2026-08-11T14:22:35.322Z", "family": "Sar\u00e9n", "given": "Tina", "initials": "T", "orcid": "0000-0001-5227-6779", "affiliations": ["Uppsala University, Dept Immunology, Genetics, Pathology, Science for Life Laboratory, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/b8f06b113565445f8dc2882a926229b6.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/b8f06b113565445f8dc2882a926229b6"}}, "publications": [{"entity": "publication", "iuid": "467d9682bec746ed878a1bacf430dbca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/467d9682bec746ed878a1bacf430dbca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/467d9682bec746ed878a1bacf430dbca"}}, "title": "Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients.", "authors": [{"family": "Sar\u00e9n", "given": "Tina", "initials": "T", "orcid": "0000-0001-5227-6779", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8f06b113565445f8dc2882a926229b6.json"}}, {"family": "Ramachandran", "given": "Mohanraj", "initials": "M", "orcid": "0000-0003-2685-0575", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3fefc78a0b040faa998efb8fde7b920.json"}}, {"family": "Gammelg\u00e5rd", "given": "Gustav", "initials": "G", "orcid": "0009-0008-5522-0103", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f8652afc79e4fe39e82bb49a5dc5307.json"}}, {"family": "L\u00f6vgren", "given": "Tanja", "initials": "T", "orcid": "0000-0003-2170-0682", "researcher": {"href": "https://publications.scilifelab.se/researcher/a578be87e95941fe8d59d344d03d1dd2.json"}}, {"family": "Mirabello", "given": "Claudio", "initials": "C", "orcid": "0000-0001-7868-034X", "researcher": {"href": "https://publications.scilifelab.se/researcher/00052b54a3d24fd4a6e648f987d15e5f.json"}}, {"family": "Bj\u00f6rklund", "given": "\u00c5sa K", "initials": "\u00c5K", "orcid": "0000-0003-2224-7090", "researcher": {"href": "https://publications.scilifelab.se/researcher/8eb8c1fc5f704cbfb87471226485ae1f.json"}}, {"family": "Wikstr\u00f6m", "given": "Kristina", "initials": "K", "orcid": "0009-0000-1027-2534", "researcher": {"href": "https://publications.scilifelab.se/researcher/0922ad45252045e9b2ac4d8ad264a718.json"}}, {"family": "Hashemi", "given": "Jamileh", "initials": "J", "orcid": "0000-0002-4997-3765", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1dd38f2d9644c1c8a9bf870fc69ef2a.json"}}, {"family": "Freyhult", "given": "Eva", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Ahlstr\u00f6m", "given": "H\u00e5kan", "initials": "H", "orcid": "0000-0002-8701-969X", "researcher": {"href": "https://publications.scilifelab.se/researcher/53e4a209929642ceaadf3e0aed6b8c69.json"}}, {"family": "Amini", "given": "Rose-Marie", "initials": "RM", "orcid": "0000-0003-0901-5252", "researcher": {"href": "https://publications.scilifelab.se/researcher/c157abcd61fa4900b5ad502b408d6d95.json"}}, {"family": "Hagberg", "given": "Hans", "initials": "H", "orcid": "0000-0001-7855-2452", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ec21157056f48e49cb2f7c528d16b1d.json"}}, {"family": "Loskog", "given": "Angelica", "initials": "A", "orcid": "0000-0001-8583-6138", "researcher": {"href": "https://publications.scilifelab.se/researcher/5730068a851041ecb0bce96c2954bb28.json"}}, {"family": "Enblad", "given": "Gunilla", "initials": "G", "orcid": "0000-0002-0594-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/11313af3f4a241ecb93af23ab2652195.json"}}, {"family": "Essand", "given": "Magnus", "initials": "M", "orcid": "0000-0002-9725-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5afc47ab0814c09909af3c66217a3a6.json"}}], "type": "journal article", "published": "2023-10-13", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "issn-l": "1078-0432", "volume": "29", "issue": "20", "pages": "4139-4152"}, "abstract": "Although CD19 chimeric antigen receptor T cells (CAR-T) therapy has shown remarkable success in B-cell malignancies, a substantial fraction of patients do not obtain a long-term clinical response. This could be influenced by the quality of the individual CAR-T infusion product. To shed some light on this, clinical outcome was correlated to characteristics of CAR-T infusion products.\n\nIn this phase II study, patients with B-cell lymphoma (n = 23) or leukemia (n = 1) received one or two infusions of third-generation CD19-directed CAR-Ts (2 \u00d7 108/m2). The clinical trial was registered at clinicaltrials.gov: NCT03068416. We investigated the transcriptional profile of individual CD19 CAR-T infusion products using targeted single-cell RNA sequencing and multicolor flow cytometry.\n\nTwo CAR-T infusions were not better than one in the settings used in this study. As for the CAR-T infusion products, we found that effector-like CD8+CAR-Ts with a high polyfunctionality, high cytotoxic and cytokine production profile, and low dysfunctional signature were associated with clinical response. An extended ex vivo expansion time during CAR-T manufacturing negatively influenced the proportion of effector CD8+CAR-Ts in the infusion product.\n\nWe identified cell-intrinsic characteristics of effector CD8+CAR-Ts correlating with response that could be used as an indicator for clinical outcome. The results in the study also serve as a guide to CAR-T manufacturing practices.", "doi": "10.1158/1078-0432.CCR-23-0178", "pmid": "37540566", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Affinity Proteomics Uppsala": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10570681"}, {"db": "pii", "key": "728314"}, {"db": "ClinicalTrials.gov", "key": "NCT03068416"}], "notes": [], "created": "2023-09-20T16:40:48.854Z", "modified": "2024-11-12T12:30:30.156Z"}, {"entity": "publication", "iuid": "0f4b2f133342404c882907cf77fe61be", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f4b2f133342404c882907cf77fe61be.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f4b2f133342404c882907cf77fe61be"}}, "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.scilifelab.se/researcher/b8f06b113565445f8dc2882a926229b6.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.scilifelab.se/researcher/c53166298a214331866c8cbf3bb9a3b9.json"}}, {"family": "Persson", "given": "Helena", "initials": "H"}, {"family": "Ramachandran", "given": "Mohanraj", "initials": "M", "orcid": "0000-0003-2685-0575", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3fefc78a0b040faa998efb8fde7b920.json"}}, {"family": "Yu", "given": "Di", "initials": "D", "orcid": "0000-0002-8636-0351", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfc1c71920c74292b4392a2ee108998d.json"}}, {"family": "Essand", "given": "Magnus", "initials": "M", "orcid": "0000-0002-9725-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5afc47ab0814c09909af3c66217a3a6.json"}}], "type": "journal article", "published": "2023-08-10", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "14", "issue": "1", "pages": "4732"}, "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": {"Global Proteomics and Proteogenomics": "Service", "Bioinformatics Support for Computational Resources": "Service", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10415375"}, {"db": "pii", "key": "10.1038/s41467-023-40303-z"}], "notes": [], "created": "2023-08-14T06:46:42.174Z", "modified": "2025-10-17T13:05:07.543Z"}]}