{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:24:38Z","timestamp":1793834678597,"version":"4.6.1"},"reference-count":65,"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>\n               <jats:p>We investigated here the novel immunomodulation and anti\u2013multiple myeloma (MM) function of T cells engaged by the bispecific T-cell engager molecule AMG 701, and further examined the impact of AMG 701 in combination with immunomodulatory drugs (IMiDs; lenalidomide and pomalidomide). AMG 701 potently induced T-cell\u2013dependent cellular cytotoxicity (TDCC) against MM cells expressing B-cell maturation antigen, including autologous cells from patients with relapsed and refractory MM (RRMM) (half maximal effective concentration, &amp;lt;46.6 pM). Besides inducing T-cell proliferation and cytolytic activity, AMG 701 also promoted differentiation of patient T cells to central memory, effector memory, and stem cell\u2013like memory (scm) phenotypes, more so in CD8 vs CD4 T subsets, resulting in increased CD8\/CD4 ratios in 7-day ex vivo cocultures. IMiDs and AMG 701 synergistically induced TDCC against MM cell lines and autologous RRMM patient cells, even in the presence of immunosuppressive bone marrow stromal cells or osteoclasts. IMiDs further upregulated AMG 701\u2013induced patient T-cell differentiation toward memory phenotypes, associated with increased CD8\/CD4 ratios, increased Tscm, and decreased interleukin 10\u2013positive T and T regulatory cells (CD25highFOXP3high), which may downregulate T effector cells. Importantly, the combination of AMG 701 with lenalidomide induced sustained inhibition of MM cell growth in SCID mice reconstituted with human T cells; tumor regrowth was eventually observed in cohorts treated with either agent alone (P &amp;lt; .001). These results strongly support AMG 701 clinical studies as monotherapy in patients with RRMM (NCT03287908) and the combination with IMiDs to improve patient outcomes in MM.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002524","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T15:41:47Z","timestamp":1599234107000},"page":"4195-4207","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":71,"title":["The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models"],"prefix":"10.1182","volume":"4","author":[{"given":"Shih-Feng","family":"Cho","sequence":"first","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"},{"name":"Division of Hematology & Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, and"},{"name":"Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Lin","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Xing","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyin","family":"Li","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"},{"name":"School of Biotechnology, Tianjin University of Science and Technology, Tianjin, People\u2019s Republic of China;"},{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Wen","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengteng","family":"Yu","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A.","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Munshi","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Wahl","sequence":"additional","affiliation":[{"name":"Amgen Research GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Matthes","sequence":"additional","affiliation":[{"name":"Amgen Research GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Amgen Research GmbH, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Arvedson","sequence":"additional","affiliation":[{"name":"Amgen Research, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth C.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-3569","authenticated-orcid":false,"given":"Yu-Tzu","family":"Tai","sequence":"additional","affiliation":[{"name":"Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 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