{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:43:13Z","timestamp":1783453393490,"version":"3.55.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"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":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bispecific T cell engaging antibodies (BiTEs) address tumor associated antigens that are over-expressed on cancer but that can also be found on healthy tissues, causing substantial on-target\/off-tumor toxicities. To overcome this hurdle, we recently introduced hemibodies, a pair of complementary antibody fragments that redirect T cells against cancer-defining antigen combinations. Here we show that hemibodies addressing CD38 and SLAMF7 recruit T cells for the exquisite elimination of dual antigen positive multiple myeloma cells while leaving single antigen positive bystanders unharmed. Moreover, CD38 and SLAMF7 targeting BiTEs, but not hemibodies induce massive cytokine release and T cell fratricide reactions, a major drawback of T cell recruiting strategies. Together, we provide evidence in vitro and in vivo that hemibodies can be developed for the effective and highly specific immunotherapy of multiple myeloma.<\/jats:p>","DOI":"10.1038\/s42003-020-01558-0","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T11:19:34Z","timestamp":1610104774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Combinatorial targeting of multiple myeloma by complementing T cell engaging antibody fragments"],"prefix":"10.1038","volume":"4","author":[{"given":"Maria","family":"Geis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6126-8954","authenticated-orcid":false,"given":"Boris","family":"Nowotny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Dominic","family":"Bohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Kouhestani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0819","authenticated-orcid":false,"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bumm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Stuhler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"1558_CR1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1053\/j.seminoncol.2016.11.004","volume":"43","author":"D Kazandjian","year":"2016","unstructured":"Kazandjian, D. Multiple myeloma epidemiology and survival: a unique malignancy. Semin. Oncol. 43, 676\u2013681 (2016).","journal-title":"Semin. Oncol."},{"key":"1558_CR2","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.3389\/fimmu.2018.01821","volume":"9","author":"SF Cho","year":"2018","unstructured":"Cho, S. F., Anderson, K. C. & Tai, Y. T. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front. Immunol. 9, 1821 (2018).","journal-title":"Front. Immunol."},{"key":"1558_CR3","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/nrclinonc.2014.200","volume":"12","author":"MA Dimopoulos","year":"2015","unstructured":"Dimopoulos, M. A. et al. Current treatment landscape for relapsed and\/or refractory multiple myeloma. Nat. Rev. Clin. Oncol. 12, 42\u201354 (2015).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1558_CR4","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1056\/NEJM199911183412102","volume":"341","author":"S Singhal","year":"1999","unstructured":"Singhal, S. et al. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341, 1565\u20131571 (1999).","journal-title":"N. Engl. J. Med."},{"key":"1558_CR5","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1056\/NEJMoa070594","volume":"357","author":"M Dimopoulos","year":"2007","unstructured":"Dimopoulos, M. et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N. Engl. J. Med. 357, 2123\u20132132 (2007).","journal-title":"N. Engl. J. Med."},{"key":"1558_CR6","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.2147\/DDDT.S115456","volume":"11","author":"R Rios-Tamayo","year":"2017","unstructured":"Rios-Tamayo, R. et al. Pomalidomide in the treatment of multiple myeloma: design, development and place in therapy. Drug Des. Dev. Ther. 11, 2399\u20132408 (2017).","journal-title":"Drug Des. Dev. Ther."},{"key":"1558_CR7","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1056\/NEJMoa030288","volume":"348","author":"PG Richardson","year":"2003","unstructured":"Richardson, P. G. et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med. 348, 2609\u20132617 (2003).","journal-title":"N. Engl. J. Med."},{"key":"1558_CR8","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1182\/blood-2016-04-711903","volume":"128","author":"SA Ali","year":"2016","unstructured":"Ali, S. A. et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 128, 1688\u20131700 (2016).","journal-title":"Blood"},{"key":"1558_CR9","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1038\/leu.2016.388","volume":"31","author":"S Hipp","year":"2017","unstructured":"Hipp, S. et al. A novel BCMA\/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia 31, 1743\u20131751 (2017).","journal-title":"Leukemia"},{"key":"1558_CR10","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1200\/JCO.19.02657","volume":"38","author":"MS Topp","year":"2020","unstructured":"Topp, M. S. et al. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. J. Clin. Oncol. 38, 775\u2013783 (2020).","journal-title":"J. Clin. Oncol."},{"key":"1558_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13196-0","volume":"10","author":"A Banaszek","year":"2019","unstructured":"Banaszek, A. et al. On-target restoration of a split T cell-engaging antibody for precision immunotherapy. Nat. Commun. 10, 5387 (2019).","journal-title":"Nat. Commun."},{"key":"1558_CR12","doi-asserted-by":"crossref","unstructured":"Brischwein, K. et al. MT110: aA novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol. Immunol. 8, 1129\u20131143 (2006).","DOI":"10.1016\/j.molimm.2005.07.034"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01558-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01558-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01558-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T19:01:23Z","timestamp":1670094083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01558-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1558"],"URL":"https:\/\/doi.org\/10.1038\/s42003-020-01558-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"assertion":[{"value":"6 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: G.S. is listed as an inventor on patent WO 2013\/104804, which is licensed to T.B. and G.S.\/Cherry Biolabs GmbH. The other authors have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44"}}