{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:23:39Z","timestamp":1787505819518,"version":"build-2736575974"},"reference-count":35,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sichuan Science and Technology Program","award":["2025ZNSFSC1693"],"award-info":[{"award-number":["2025ZNSFSC1693"]}]},{"name":"Sichuan Science and Technology Program","award":["2025ZNSFSC1695"],"award-info":[{"award-number":["2025ZNSFSC1695"]}]},{"name":"Central Government Guidance Funds for Local Science and Technology Development","award":["2023ZYDF070"],"award-info":[{"award-number":["2023ZYDF070"]}]},{"name":"Central Government Guidance Funds for Local Science and Technology Development","award":["2023ZYDF097"],"award-info":[{"award-number":["2023ZYDF097"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["GZC20241136"],"award-info":[{"award-number":["GZC20241136"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postdoctoral Research Fund of West China Hospital, Sichuan University","award":["2024HXBH097"],"award-info":[{"award-number":["2024HXBH097"]}]},{"name":"the Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation","award":["2025ZH032"],"award-info":[{"award-number":["2025ZH032"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471551"],"award-info":[{"award-number":["32471551"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82500302"],"award-info":[{"award-number":["82500302"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3403303"],"award-info":[{"award-number":["2023YFC3403303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,2,4]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple myeloma (MM) is a hematologic malignancy characterized by a high relapse rate despite recent therapeutic advances. B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) are two well-validated targets, with Food and Drug Administration-approved bispecific antibodies demonstrating clinical efficacy; however, their effectiveness is often limited by antigen escape and immune evasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study presents a novel humanized trispecific antibody, YMN-V115, designed in a 1+1+1 format with one binding site each for BCMA, GPRC5D, and CD3. This structural configuration was strategically selected to maximize tumor-specific T cell engagement through dual-antigen targeting while minimizing the risk of CD3-mediated off-tumor toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      YMN-V115 exhibited superior cytotoxic activity against MM cells in both in vitro and in vivo models, outperforming its bispecific counterparts. Notably, its efficacy was maintained under soluble BCMA-saturated conditions, demonstrating resistance to decoy inhibition. Moreover, YMN-V115 effectively addressed antigenic heterogeneity by targeting both BCMA\n                      <jats:sup>+<\/jats:sup>\n                      and GPRC5D\n                      <jats:sup>+<\/jats:sup>\n                      tumor subsets, resulting in enhanced T-cell activation and durable tumor control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>YMN-V115 represents a next-generation trispecific T-cell engager that effectively addresses antigenic heterogeneity and immune evasion in MM. These preclinical findings support its further clinical development as a promising therapeutic strategy for relapsed or refractory MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013986","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T15:20:19Z","timestamp":1771428019000},"page":"e013986","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["YMN-V115: a novel humanized BCMA\/GPRC5D\/CD3 trispecific antibody in relapsed\/refractory multiple myeloma"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03399799","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2692-1813","authenticated-orcid":false,"given":"Jia","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, 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Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongdong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqing","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China 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