{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:39:21Z","timestamp":1790847561269,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2012.113.2"],"award-info":[{"award-number":["2012.113.2"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1192B5"],"award-info":[{"award-number":["SFB1192B5"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jose Carreras Leuk\u00e4mie-Stiftung, Deutsche Gesellschaft f\u00fcr H\u00e4matologie und Onkologie","award":["180302"],"award-info":[{"award-number":["180302"]}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["111303"],"award-info":[{"award-number":["111303"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The NAD-hydrolyzing ecto-enzyme CD38 is overexpressed by multiple myeloma and other hematological malignancies. We recently generated CD38-specific nanobodies, single immunoglobulin variable domains derived from heavy-chain antibodies naturally occurring in llamas. Nanobodies exhibit high solubility and stability, allowing easy reformatting into recombinant fusion proteins. Here we explore the utility of CD38-specific nanobodies as ligands for nanobody-based chimeric antigen receptors (Nb-CARs). We cloned retroviral expression vectors for CD38-specific Nb-CARs. The human natural killer cell line NK-92 was transduced to stably express these Nb-CARs. As target cells we used CD38-expressing as well as CRISPR\/Cas9-generated CD38-deficient tumor cell lines (CA-46, LP-1, and Daudi) transduced with firefly luciferase. With these effector and target cells we established luminescence and flow-cytometry CAR-dependent cellular cytotoxicity assays (CARDCCs). Finally, the cytotoxic efficacy of Nb-CAR NK-92 cells was tested on primary patient-derived CD38-expressing multiple myeloma cells. NK-92 cells expressing CD38-specific Nb-CARs specifically lysed CD38-expressing but not CD38-deficient tumor cell lines. Moreover, the Nb-CAR-NK cells effectively depleted CD38-expressing multiple myeloma cells in primary human bone marrow samples. Our results demonstrate efficacy of Nb-CARs in vitro. The potential clinical efficacy of Nb-CARs in vivo remains to be evaluated.<\/jats:p>","DOI":"10.3390\/cells9020321","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T10:51:07Z","timestamp":1580295067000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Targeting CD38-Expressing Multiple Myeloma and Burkitt Lymphoma Cells In Vitro with Nanobody-Based Chimeric Antigen Receptors (Nb-CARs)"],"prefix":"10.3390","volume":"9","author":[{"given":"Julia","family":"Hambach","sequence":"first","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-6766","authenticated-orcid":false,"given":"Kristoffer","family":"Riecken","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, UKE, 20246 Hamburg, Germany"},{"name":"Department of Stem Cell Transplantation, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Cichutek","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, UKE, 20246 Hamburg, Germany"},{"name":"Department of Stem Cell Transplantation, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Sch\u00fctze","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Petry","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana Larissa","family":"R\u00f6ckendorf","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Baum","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaus","family":"Kr\u00f6ger","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Hansen","sequence":"additional","affiliation":[{"name":"Hematological-Oncology Center Altona, 22767 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Schuch","sequence":"additional","affiliation":[{"name":"Hematological-Oncology Center Altona, 22767 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Haag","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-7211","authenticated-orcid":false,"given":"Boris","family":"Fehse","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, UKE, 20246 Hamburg, Germany"},{"name":"Department of Stem Cell Transplantation, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-534X","authenticated-orcid":false,"given":"Peter","family":"Bannas","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, UKE, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Koch-Nolte","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molmed.2008.02.005","article-title":"CD38 at the junction between prognostic marker and therapeutic 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Sci., 19.","DOI":"10.3390\/ijms19020403"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/321\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:52:55Z","timestamp":1760172775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,29]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["cells9020321"],"URL":"https:\/\/doi.org\/10.3390\/cells9020321","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,29]]}}}