{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:24:41Z","timestamp":1793834681645,"version":"4.6.1"},"reference-count":50,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple myeloma (MM) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (PCs) in the bone marrow (BM). Patient outcome may be improved with BiTE (bispecific T-cell engager) molecules, which redirect T cells to lyse tumor cells. B-cell maturation antigen (BCMA) supports PC survival and is highly expressed on MM cells. A half-life extended anti-BCMA BiTE molecule (AMG 701) induced selective cytotoxicity against BCMA-expressing MM cells (average half-maximal effective concentration, 18.8 \u00b1 14.8 pM), T-cell activation, and cytokine release in vitro. In a subcutaneous mouse xenograft model, at all doses tested, AMG 701 completely inhibited tumor formation (P &amp;lt; .001), as well as inhibited growth of established tumors (P \u2264 .001) and extended survival in an orthotopic MM model (P \u2264 .01). To evaluate AMG 701 bioactivity in cynomolgus monkeys, a PC surface phenotype and specific genes were defined to enable a quantitative digital droplet polymerase chain reaction assay (sensitivity, 0.1%). Dose-dependent pharmacokinetic and pharmacodynamic behavior was observed, with depletion of PC-specific genes reaching 93% in blood and 85% in BM. Combination with a programmed cell death protein 1 (PD-1)\u2013blocking antibody significantly increased AMG 701 potency in vitro. A model of AMG 701 binding to BCMA and CD3 indicates that the distance between the T-cell and target cell membranes (ie, the immunological synapse) is similar to that of the major histocompatibility complex class I molecule binding to a T-cell receptor and suggests that the synapse would not be disrupted by the half-life extending Fc domain. These data support the clinical development of AMG 701.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002565","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T15:40:31Z","timestamp":1599234031000},"page":"4180-4194","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":52,"title":["AMG 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys"],"prefix":"10.1182","volume":"4","author":[{"given":"Rebecca L.","family":"Goldstein","sequence":"first","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6962-727X","authenticated-orcid":false,"given":"Ana","family":"Goyos","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-5652","authenticated-orcid":false,"given":"Chi-Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Deegen","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Bogner","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Sternjak","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Thomas","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Klinger","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Wahl","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benno","family":"Rattel","sequence":"additional","affiliation":[{"name":"Amgen Research (Munich) GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Lamas","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., Thousand Oaks, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshan","family":"Min","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Sudom","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mozhgan","family":"Farshbaf","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Coxon","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., Thousand Oaks, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedesz","family":"Balazs","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Arvedson","sequence":"additional","affiliation":[{"name":"Amgen Research, Amgen Inc., South San Francisco, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"issue":"1","key":"2020090412394885000_B1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrclinonc.2014.200","article-title":"Current treatment landscape for relapsed and\/or refractory multiple myeloma","volume":"12","author":"Dimopoulos","year":"2015","journal-title":"Nat Rev Clin Oncol"},{"issue":"1","key":"2020090412394885000_B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21387","article-title":"Cancer Statistics, 2017","volume":"67","author":"Siegel","year":"2017","journal-title":"CA Cancer J Clin"},{"key":"2020090412394885000_B3","unstructured":"Howlader N , NooneAM, KrapchoM, MillerD, et al In: Cronin KA, eds. 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