{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:43:11Z","timestamp":1792244591707,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","award":["2024\u2010001"],"award-info":[{"award-number":["2024\u2010001"]}],"id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Despite advances in terms of bispecific antibodies (BsAbs) targeting single tumor\u2010associated antigens in multiple myeloma (MM), not all patients respond, and most eventually relapse. Using flow cytometry, we found that BCMA and GPRC5D expression is highly heterogeneous within and between patients. Dual targeting with ramantamig (JNJ\u201079635322), a trispecific antibody targeting both BCMA and GPRC5D on the tumor cell surface, has been hypothesized to improve efficacy by overcoming heterogeneous target expression and preventing resistance due to antigen escape. Using T\u2010cells from healthy donors, ramantamig was significantly more effective than mono\u2010targeting antibodies against BCMA\n                    <jats:sup>+<\/jats:sup>\n                    GPRC5D\n                    <jats:sup>+<\/jats:sup>\n                    MM cell lines, and also efficiently eliminated single antigen\u2010positive MM cell lines. Additionally, ramantamig effectively induced MM cell lysis in 32 BM samples from MM patients (mean lysis with 0.4\u2009nM: 60%), demonstrating superior cytotoxic activity compared to BCMA\u2010 and GPRC5D\u2010mono\u2010targeting BsAbs (13% and 5%, respectively). There was no difference in ramantamig\u2010mediated lysis of MM cells from newly diagnosed or heavily pretreated, BsAb\u2010na\u00efve patients. Importantly, tumor cell target expression was an important determinant of\n                    <jats:italic>ex vivo<\/jats:italic>\n                    response, shown by superior MM cell lysis in samples with higher than median baseline proportion of GPRC5D\/BCMA double\u2010antigen\u2010positive MM cells, when compared to lower GPRC5D\/BCMA expression. Notably, ramantamig potency was less affected by the presence of soluble BCMA, compared to the BCMA\u2010mono\u2010targeting control antibody. Finally, ramantamig showed superior potency, compared to the combination of two single\u2010targeted BsAbs, probably due to higher avidity against heterogeneous targets. In conclusion, dual\u2010antigen targeting with ramantamig represents a significant advancement in overcoming tumor heterogeneity and preventing antigen escape\u2010mediated resistance.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70487","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:01:31Z","timestamp":1791381691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual targeting of BCMA and GPRC5D with the trispecific antibody ramantamig addresses antigenic heterogeneity in myeloma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-2932","authenticated-orcid":false,"given":"Chloe","family":"O'Neill","sequence":"first","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marloes E. C.","family":"Broekmans","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0191-4343","authenticated-orcid":false,"given":"Charlotte L. B. M.","family":"Korst","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Krevvata","sequence":"additional","affiliation":[{"name":"Johnson&amp;Johnson Spring House Pennsylvania United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Dal Collo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-8908","authenticated-orcid":false,"given":"Serena R.","family":"Baglio","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Philippar","sequence":"additional","affiliation":[{"name":"Johnson&amp;Johnson Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodandaram","family":"Pillarisetti","sequence":"additional","affiliation":[{"name":"Johnson&amp;Johnson Spring House Pennsylvania United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeksha","family":"Vishwamitra","sequence":"additional","affiliation":[{"name":"Johnson&amp;Johnson Spring House Pennsylvania United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-7187","authenticated-orcid":false,"given":"Tuna","family":"Mutis","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-2603","authenticated-orcid":false,"given":"Niels W. 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