{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:20:37Z","timestamp":1793622037675,"version":"4.5.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20<jats:sup>+<\/jats:sup> tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed\/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma (<jats:italic>n<\/jats:italic>\u2009=\u200916), follicular lymphoma (<jats:italic>n<\/jats:italic>\u2009=\u200915), and mantle cell lymphoma (<jats:italic>n<\/jats:italic>\u2009=\u20098), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed\/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies.<\/jats:p>","DOI":"10.1038\/s41408-021-00430-6","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T09:06:15Z","timestamp":1613811975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-1138","authenticated-orcid":false,"given":"Hilma J.","family":"van der Horst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-1762","authenticated-orcid":false,"given":"A. Vera","family":"de Jonge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida H.","family":"Hiemstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne T.","family":"Gelderloos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella R. A. I.","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie J.","family":"Hijmering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik F.","family":"van Essen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9725-4060","authenticated-orcid":false,"given":"Daphne","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine E. D.","family":"Chamuleau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5368-6849","authenticated-orcid":false,"given":"Esther C. 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Cell Biol. 93, 290\u2013296 (2015).","journal-title":"Immunol. Cell Biol."},{"key":"430_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/srep17943","volume":"5","author":"EJ Smith","year":"2015","unstructured":"Smith, E. J. et al. A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys. Sci. Rep. 5, 17943 (2015).","journal-title":"Sci. Rep."},{"key":"430_CR6","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1002\/ijc.23626","volume":"123","author":"M Stanglmaier","year":"2008","unstructured":"Stanglmaier, M. et al. Bi20 (fBTA05), a novel trifunctional bispecific antibody (anti-CD20 x anti-CD3), mediates efficient killing of B-cell lymphoma cells even with very low CD20 expression levels. Int. J. Cancer 123, 1181\u20131189 (2008).","journal-title":"Int. J. 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CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood 119, 3940\u20133950 (2012).","journal-title":"Blood"},{"key":"430_CR10","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/CJI.0000000000000199","volume":"41","author":"SY Lee","year":"2018","unstructured":"Lee, S. Y. et al. Preclinical optimization of a CD20-specific chimeric antigen receptor vector and culture conditions. J. Immunother. 41, 19\u201331 (2018).","journal-title":"J. Immunother."},{"key":"430_CR11","doi-asserted-by":"publisher","first-page":"287ra70","DOI":"10.1126\/scitranslmed.aaa4802","volume":"7","author":"LL Sun","year":"2015","unstructured":"Sun, L. L. et al. Anti-CD20\/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci. Transl. Med. 7, 287ra70 (2015).","journal-title":"Sci. Transl. 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Epcoritamab (GEN3013; DuoBody-CD3\u00d7CD20) to induce complete response in patients with relapsed\/refractory B-cell non-Hodgkin lymphoma (B-NHL): complete dose escalation data and efficacy results from a phase I\/II trial. J. Clin. Oncol. 38, 8009 (2020).","journal-title":"J. Clin. Oncol."},{"key":"430_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.1","volume":"5","author":"ZZ Yang","year":"2015","unstructured":"Yang, Z. Z. et al. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 5, e281 (2015).","journal-title":"Blood Cancer J."},{"key":"430_CR16","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1093\/annonc\/mdg201","volume":"14","author":"J Mangel","year":"2003","unstructured":"Mangel, J. et al. 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H.J.H., M.E.C., E.C.W.B., and T.M. are inventors on Genmab patent applications. I.H.H. and E.C.W.B. own Genmab warrants and\/or stock.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"38"}}