{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:28:22Z","timestamp":1792643302493,"version":"4.5.0"},"reference-count":66,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"664","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,9,28]]},"abstract":"<jats:p>\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    is a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells that respond to\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    are present in the endogenous repertoire of patients with IPA but are infrequent and cannot be consistently isolated and expanded for adoptive immunotherapy. Therefore, we gene-engineered\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    \u2013specific chimeric antigen receptor (Af-CAR) T cells and demonstrate their ability to confer antifungal reactivity in preclinical models in vitro and in vivo. We generated a CAR targeting domain AB90-E8 that recognizes a conserved protein antigen in the cell wall of\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    hyphae. T cells expressing the Af-CAR recognized\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    strains and clinical isolates and exerted a direct antifungal effect against\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    hyphae. In particular, CD8\n                    <jats:sup>+<\/jats:sup>\n                    Af-CAR T cells released perforin and granzyme B and damaged\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    hyphae. CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    Af-CAR T cells produced cytokines that activated macrophages to potentiate the antifungal effect. In an in vivo model of IPA in immunodeficient mice, CD8\n                    <jats:sup>+<\/jats:sup>\n                    Af-CAR T cells localized to the site of infection, engaged innate immune cells, and reduced fungal burden in the lung. Adoptive transfer of CD8\n                    <jats:sup>+<\/jats:sup>\n                    Af-CAR T cells conferred greater antifungal efficacy compared to CD4\n                    <jats:sup>+<\/jats:sup>\n                    Af-CAR T cells and an improvement in overall survival. Together, our study illustrates the potential of gene-engineered T cells to treat aggressive infectious diseases that are difficult to control with conventional antimicrobial therapy and support the clinical development of Af-CAR T cell therapy to treat IPA.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abh1209","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T13:58:43Z","timestamp":1664373523000},"source":"Crossref","is-referenced-by-count":116,"title":["CAR T cells targeting\n                    <i>Aspergillus fumigatus<\/i>\n                    are effective at treating invasive pulmonary aspergillosis in preclinical models"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6318-7680","authenticated-orcid":true,"given":"Michelle","family":"Seif","sequence":"first","affiliation":[{"name":"Medizinische Klinik und Poliklinik II und Lehrstuhl f\u00fcr Zellul\u00e4re Immuntherapie, Medizinische Klinik und Poliklinik II, Universit\u00e4tsklinikum W\u00fcrzburg, 97080 W\u00fcrzburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-3916","authenticated-orcid":true,"given":"Tamara Katharina","family":"Kakoschke","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Mund-, Kiefer- und Gesichtschirurgie, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, 80337 M\u00fcnchen, Germany."},{"name":"Institut f\u00fcr Infektionsmedizin und Zoonosen, Medizinische Fakult\u00e4t, LMU, 80539 M\u00fcnchen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ebel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Infektionsmedizin und Zoonosen, Medizinische Fakult\u00e4t, LMU, 80539 M\u00fcnchen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7604-0189","authenticated-orcid":true,"given":"Marina Maria","family":"Bellet","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8859-3386","authenticated-orcid":true,"given":"Nora","family":"Trinks","sequence":"additional","affiliation":[{"name":"Lehrstuhl f\u00fcr Biotechnologie und Biophysik, Biozentrum und RVZ - Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universit\u00e4t W\u00fcrzburg, 97074 W\u00fcrzburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9762-6493","authenticated-orcid":true,"given":"Giorgia","family":"Renga","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9896-171X","authenticated-orcid":true,"given":"Marilena","family":"Pariano","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Romani","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1099-7871","authenticated-orcid":true,"given":"Beeke","family":"Tappe","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik II und Lehrstuhl f\u00fcr Zellul\u00e4re Immuntherapie, Medizinische Klinik und Poliklinik II, Universit\u00e4tsklinikum W\u00fcrzburg, 97080 W\u00fcrzburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Espie","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Institut Cochin, INSERM, CNRS, 75014 Paris, France."},{"name":"CAR-T Cells Department, Invectys, 75013 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-7254","authenticated-orcid":true,"given":"Emmanuel","family":"Donnadieu","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Institut Cochin, INSERM, CNRS, 75014 Paris, France."},{"name":"Equipe labellis\u00e9e Ligue Contre le Cancer, 75014 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-0484","authenticated-orcid":true,"given":"Kerstin","family":"H\u00fcnniger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Hygiene und Mikrobiologie, Julius-Maximilians-Universit\u00e4t W\u00fcrzburg, 97080 W\u00fcrzburg, Germany."},{"name":"Fungal Septomics Research Group, Leibniz-Institut f\u00fcr Naturstoff-Forschung und Infektionsbiologie \u2013 Hans-Kn\u00f6ll-Institut (HKI), 07743 Jena, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-1754","authenticated-orcid":true,"given":"Antje","family":"H\u00e4der","sequence":"additional","affiliation":[{"name":"Fungal Septomics Research Group, Leibniz-Institut f\u00fcr Naturstoff-Forschung und Infektionsbiologie \u2013 Hans-Kn\u00f6ll-Institut (HKI), 07743 Jena, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-3219","authenticated-orcid":true,"given":"Markus","family":"Sauer","sequence":"additional","affiliation":[{"name":"Lehrstuhl f\u00fcr Biotechnologie und Biophysik, Biozentrum und RVZ - 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