{"entity": "researcher", "timestamp": "2026-07-12T08:17:57.872Z", "family": "Essand", "given": "Magnus", "initials": "M", "orcid": "0000-0002-9725-0422", "affiliations": ["Uppsala University, Dept Immunology, Genetics, Pathology, Science for Life Laboratory, Uppsala, Sweden. magnus.essand@igp.uu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c5afc47ab0814c09909af3c66217a3a6.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c5afc47ab0814c09909af3c66217a3a6"}}, "publications": [{"entity": "publication", "iuid": "f09706baf2a74636a49097f82b60b681", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f09706baf2a74636a49097f82b60b681.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f09706baf2a74636a49097f82b60b681"}}, "title": "VLDLR mediates Semliki Forest virus neuroinvasion through the blood-cerebrospinal fluid barrier.", "authors": [{"family": "Martikainen", "given": "Miika", "initials": "M", "orcid": "0000-0001-8202-701X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3477399dd7474fc6a18863b4c239d81c.json"}}, {"family": "Lugano", "given": "Roberta", "initials": "R"}, {"family": "Pietil\u00e4", "given": "Ilkka", "initials": "I"}, {"family": "Brosch", "given": "Sofie", "initials": "S"}, {"family": "Cabrolier", "given": "Camille", "initials": "C"}, {"family": "Sivaramakrishnan", "given": "Aishwarya", "initials": "A"}, {"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": "Dimberg", "given": "Anna", "initials": "A", "orcid": "0000-0003-4422-9125", "researcher": {"href": "https://publications.scilifelab.se/researcher/c53166298a214331866c8cbf3bb9a3b9.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": "2024-12-23", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "10718", "issn-l": "2041-1723"}, "abstract": "Semliki Forest virus (SFV) is a neuropathogenic alphavirus which is of interest both as a model neurotropic alphavirus and as an oncolytic virus with proven potency in preclinical cancer models. In laboratory mice, peripherally administered SFV infiltrates the central nervous system (CNS) and causes encephalitis of varying severity. The route of SFV CNS entrance is poorly understood but has been considered to occur through the blood-brain barrier. Here we show that neuroinvasion of intravenously administered SFV is strictly dependent on very-low-density-lipoprotein receptor (VLDLR) which acts as an entry receptor for SFV. Moreover, SFV primarily enters the CNS through the blood-cerebrospinal fluid (B-CSF) barrier via infecting choroid plexus epithelial cells which show distinctly high expression of VLDLR. This is the first indication of neurotropic alphavirus utilizing choroid plexus for CNS entry, and VLDLR playing a specific and crucial role for mediating SFV entry through this pathway.", "doi": "10.1038/s41467-024-55493-3", "pmid": "39715740", "labels": {"Bioinformatics Support for Computational Resources": "Service", "CRISPR Functional Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11666578"}, {"db": "pii", "key": "10.1038/s41467-024-55493-3"}, {"db": "GEO", "key": "GSE283607"}], "notes": [], "created": "2025-02-28T14:14:51.638Z", "modified": "2025-09-15T09:21:34.660Z"}, {"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"}]}