{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:43:46Z","timestamp":1792122226879,"version":"4.4.0"},"reference-count":87,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Malaysia Ministry of Higher Education Fundamental Research","award":["FRGS\/1\/2025\/SKK06\/UM\/ (FP015-2025)"],"award-info":[{"award-number":["FRGS\/1\/2025\/SKK06\/UM\/ (FP015-2025)"]}]},{"name":"Malaysia Ministry of Higher Education Fundamental Research","award":["FRGS\/1\/2019\/SKK06\/UM\/02\/11 (FP134-2019A)"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK06\/UM\/02\/11 (FP134-2019A)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessive production of monoclonal immunoglobulins, leading to end-organ damage such as osteolytic bone lesions. Despite substantial therapeutic progress achieved with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, multiple myeloma remains incurable, and outcomes for triple-class-refractory patients remain dismal, with median survival below one year. Bispecific T cell engaging antibodies (TCEs) have recently emerged as a promising immunotherapeutic approach capable of redirecting cytotoxic T cells to eliminate malignant plasma cells. These engineered antibodies simultaneously engage CD3 on T cells and a tumor-associated antigen such as B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D), or Fc receptor homolog 5 (FcRH5), thereby forming an immune synapse that triggers T cell activation, cytokine secretion, and perforin\u2013granzyme-mediated apoptosis of the targeted B cell. This review summarizes the molecular design, mechanism of action, and clinical development of TCEs in MM, encompassing early bi-specific T cell engagers (BiTE) constructs such as AMG 420 and next-generation IgG-like molecules including teclistamab. Pivotal clinical trials have demonstrated overall response rates between 43% and 73%, accompanied by durable remissions and manageable safety profiles. Future directions include earlier-line integration, synergistic combinations with immunomodulatory or costimulatory agents, and the development of trispecific formats to overcome antigen escape and T cell exhaustion. Collectively, TCEs represent a paradigm shift toward durable, immune-mediated disease control in multiple myeloma.<\/jats:p>","DOI":"10.3390\/medicina61122113","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T11:50:13Z","timestamp":1764244213000},"page":"2113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanistic Insights and Advances of Bispecific T Cell Engaging Antibodies Therapy in Multiple Myeloma"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0981-9626","authenticated-orcid":false,"given":"Ting Fang","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-4955","authenticated-orcid":false,"given":"Chin Sum","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4830-3495","authenticated-orcid":false,"given":"Chung Yeng","family":"Looi","sequence":"additional","affiliation":[{"name":"School of Biosciences, Faculty of Health & Medical Sciences, Taylor\u2019s University, Subang Jaya 47500, Malaysia"},{"name":"Digital Health and Medical Advancement Impact Lab, Taylor\u2019s University, Subang Jaya 47500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-1956","authenticated-orcid":false,"given":"Won Fen","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2129-782X","authenticated-orcid":false,"given":"Gin Gin","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/ajh.26590","article-title":"Multiple myeloma: 2022 update on diagnosis, risk stratification, and management","volume":"97","author":"Rajkumar","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104594","DOI":"10.1016\/j.cellimm.2022.104594","article-title":"Regulatory network of BLIMP1, IRF4, and XBP1 triad in plasmacytic differentiation and multiple myeloma pathogenesis","volume":"380","author":"Tang","year":"2022","journal-title":"Cell Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tang, T.F., Chan, Y.T., Lim, H.J., Cheok, Y.Y., Anuar, N.A., Cheong, C.S., Looi, C.Y., Tan, S.M., Wong, W.F., and Gan, G.G. (2025). RUNX1 expression dynamics in plasma cell differentiation and pathogenesis of multiple myeloma. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1643615"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1002\/eji.201141553","article-title":"Alternate pathways for Bcl6-mediated regulation of B cell to plasma cell differentiation","volume":"41","author":"Alinikula","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41588-025-02196-0","article-title":"Genomic landscape of multiple myeloma and its precursor conditions","volume":"57","author":"Alberge","year":"2025","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1038\/s41467-019-11680-1","article-title":"Genomic landscape and chronological reconstruction of driver events in multiple myeloma","volume":"10","author":"Maura","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e207","DOI":"10.1038\/bcj.2014.29","article-title":"The role of epigenetics in the biology of multiple myeloma","volume":"4","author":"Dimopoulos","year":"2014","journal-title":"Blood Cancer J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/wsbm.89","article-title":"DNA methylation alterations in multiple myeloma as a model for epigenetic changes in cancer","volume":"2","author":"Sharma","year":"2010","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41375-018-0300-0","article-title":"MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells","volume":"33","author":"Xie","year":"2019","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Popovic, R., Martinez-Garcia, E., Giannopoulou, E.G., Zhang, Q., Zhang, Q., Ezponda, T., Shah, M.Y., Zheng, Y., Will, C.M., and Small, E.C. (2014). Histone methyltransferase MMSET\/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004566"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa1903455","article-title":"Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma","volume":"381","author":"Chari","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1080\/10428194.2024.2411625","article-title":"The landscape of clinical trials for heavily pretreated multiple myeloma: Opportunity for more randomization?","volume":"66","author":"Kapur","year":"2025","journal-title":"Leuk. Lymphoma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1080\/10428194.2024.2408646","article-title":"Optimizing multiple Myeloma clinical trials: Research direction, addressing limitations, and strategies for improvement","volume":"66","author":"Ebraheem","year":"2025","journal-title":"Leuk. Lymphoma"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lytvynova, O., Jwayyed, J., Pastel, D., Prasad, R., Khouri, J., Williams, L., Mazzoni, S., Raza, S., and Anwer, F. (2024). Insights from Clinical Trials: Evidence-Based Recommendations for Induction Treatment of Newly Diagnosed Transplant-Eligible Multiple Myeloma. Antibodies, 13.","DOI":"10.20944\/preprints202408.0994.v1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.1002\/hem3.132","article-title":"Prophylactic tocilizumab reduces the incidence of cytokine release syndrome in relapsed\/refractory myeloma patients treated with teclistamab: Implications for outpatient step-up dosing","volume":"8","author":"Korst","year":"2024","journal-title":"Hemasphere"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41408-023-00963-y","article-title":"Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience","volume":"13","author":"Scott","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/JLB.MR0718-269R","article-title":"Mechanisms of natural killer cell-mediated cellular cytotoxicity","volume":"105","author":"Prager","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/sj.cdd.4402244","article-title":"Mechanisms of granule-dependent killing","volume":"15","author":"Cullen","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1038\/s41375-018-0014-3","article-title":"Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation","volume":"32","author":"Correnti","year":"2018","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e003354","DOI":"10.1136\/jitc-2021-003354","article-title":"4-1BB and optimized CD28 co-stimulation enhances function of human mono-specific and bi-specific third-generation CAR T cells","volume":"9","author":"Roselli","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41408-022-00766-7","article-title":"Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice: Results from the NEUF study","volume":"13","author":"Boissel","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1470-2045(14)71170-2","article-title":"Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: A multicentre, single-arm, phase 2 study","volume":"16","author":"Topp","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1080\/10428194.2025.2528115","article-title":"BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: A phase 1b open-label expansion study","volume":"66","author":"Rodriguez","year":"2025","journal-title":"Leuk. Lymphoma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1200\/JCO.19.02657","article-title":"Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma","volume":"38","author":"Topp","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1111\/jcpt.13741","article-title":"The pharmacology of blinatumomab: State of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials","volume":"47","author":"Mocquot","year":"2022","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s40262-016-0405-4","article-title":"Blinatumomab, a Bispecific T-cell Engager (BiTE((R))) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications","volume":"55","author":"Zhu","year":"2016","journal-title":"Clin. Pharmacokinet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00262-024-03913-0","article-title":"Targeting BCMA in multiple myeloma: Designs, challenges, and future directions","volume":"74","author":"Hu","year":"2025","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1182\/bloodadvances.2020002565","article-title":"AMG 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys","volume":"4","author":"Goldstein","year":"2020","journal-title":"Blood Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2147\/JBM.S507550","article-title":"Matching-Adjusted Indirect Comparison of Elranatamab versus Teclistamab in Patients with Triple-Class Exposed\/Refractory Multiple Myeloma: Updated Results","volume":"16","author":"Mol","year":"2025","journal-title":"J. Blood Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(21)01338-6","article-title":"Teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): A multicentre, open-label, single-arm, phase 1 study","volume":"398","author":"Usmani","year":"2021","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa2203478","article-title":"Teclistamab in Relapsed or Refractory Multiple Myeloma","volume":"387","author":"Moreau","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1038\/s41591-023-02528-9","article-title":"Elranatamab in relapsed or refractory multiple myeloma: Phase 2 MagnetisMM-3 trial results","volume":"29","author":"Lesokhin","year":"2023","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1002\/hem3.136","article-title":"Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM-3 study","volume":"8","author":"Tomasson","year":"2024","journal-title":"Hemasphere"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/14712598.2025.2465825","article-title":"An evaluation of linvoseltamab for treatment of relapsed\/refractory multiple myeloma","volume":"25","author":"Avigan","year":"2025","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, H.C., Bumma, N., Richter, J., Zonder, J.A., Hoffman, J.E., Zhou, Z.Y., Garcia-Horton, V., Fillbrunn, M., Wang, H., and Mattera, M. (2025). Indirect Comparison of Linvoseltamab Versus Teclistamab for the Treatment of Triple-Class Exposed Relapsed\/Refractory Multiple Myeloma. Clin. Lymphoma Myeloma Leuk., 25.","DOI":"10.1016\/S2152-2650(25)03517-7"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1220745","DOI":"10.1097\/01.HS9.0000970436.12207.45","article-title":"Alnuctamab (ALNUC.; BMS-986349; CC-93269), a BCMA \u00d7 CD3 T-Cell Engager, in Patients (PTS) with Relapsed\/Refractory Multiple Myeloma (RRMM): Latest Results from a Phase 1 First-In-Human Clinical Study","volume":"7","author":"Wong","year":"2023","journal-title":"HemaSphere"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1182\/blood-2022-159009","article-title":"Alnuctamab (ALNUC.; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) \u00d7 CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed\/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study","volume":"140","author":"Wong","year":"2022","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.clml.2023.11.001","article-title":"Teclistamab Improves Patient-Reported Symptoms and Health-Related Quality of Life in Relapsed or Refractory Multiple Myeloma: Results from the Phase II MajesTEC-1 Study","volume":"24","author":"Martin","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1182\/blood-2024-205608","article-title":"Phase 3 Study of Teclistamab (Tec) in Combination with Lenalidomide (Len) and Tec Alone Versus Len Alone in Newly Diagnosed Multiple Myeloma (NDMM) As Maintenance Therapy Following Autologous Stem Cell Transplantation (ASCT): Safety Run-in (SRI) Results from the Majestec-4\/EMN30 Trial","volume":"144","author":"Zamagni","year":"2024","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e70224","DOI":"10.1002\/hem3.70224","article-title":"The impact of reduced dosing frequency of elranatamab on patient-reported outcomes in patients with relapsed or refractory multiple myeloma: Results from MagnetisMM-3","volume":"9","author":"Bahlis","year":"2025","journal-title":"Hemasphere"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1200\/JCO.24.01008","article-title":"Linvoseltamab for Treatment of Relapsed\/Refractory Multiple Myeloma","volume":"42","author":"Bumma","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/cpt.3353","article-title":"Informing the Recommended Phase III Dose of Alnuctamab, a CD3 \u00d7 BCMA T-Cell Engager, Using Population Pharmacokinetics and Exposure-Response Analysis","volume":"116","author":"Kiesel","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1182\/bloodadvances.2020003805","article-title":"Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma","volume":"5","author":"Verkleij","year":"2021","journal-title":"Blood Adv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1177\/10600280241271192","article-title":"Targeting GPRC5D With Talquetamab: A New Frontier in Bispecific Antibody Therapy for Relapsed\/Refractory Multiple Myeloma","volume":"59","author":"Shaver","year":"2025","journal-title":"Ann. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1182\/blood-2024-199542","article-title":"Cevostamab in Patients with Heavily Pretreated Relapsed\/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies","volume":"44","author":"Richter","year":"2024","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/14737140.2024.2344647","article-title":"Antibody-drug conjugates, bispecific antibodies and CAR-T cells therapy in multiple myeloma","volume":"24","author":"Tacchetti","year":"2024","journal-title":"Expert. Rev. Anticancer. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1080\/14712598.2020.1802422","article-title":"Antibody-drug conjugates for multiple myeloma","volume":"21","author":"McMillan","year":"2021","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2147\/OTT.S398118","article-title":"The Role of CELMoD Agents in Multiple Myeloma","volume":"18","author":"Bahlis","year":"2025","journal-title":"Onco Targets Ther."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Meermeier, E.W., Pfeffer, K., Stein, C.K., Sharik, M., Du, M.T., Tafoya Alvarado, Y., Shi, C.X., Zhu, Y.X., Bergsagel, P.L., and Chesi, M. (2025). An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden. Blood.","DOI":"10.1182\/blood.2025029215"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1186\/s12964-025-02443-1","article-title":"CAR-NK cell therapy in multiple myeloma: From preclinical and clinical landscape to joining the force for treatment strategies optimization","volume":"23","author":"Yazdanparast","year":"2025","journal-title":"Cell Commun. Signal"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"109168","DOI":"10.1016\/j.clim.2022.109168","article-title":"NK cell therapy in relapsed refractory multiple myeloma","volume":"246","author":"Roshandel","year":"2023","journal-title":"Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41408-025-01334-5","article-title":"Comprehensive assessment of adverse event profiles associated with bispecific antibodies in multiple myeloma","volume":"15","author":"Golmohammadi","year":"2025","journal-title":"Blood Cancer J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1016\/S1470-2045(23)00159-6","article-title":"Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: A consensus report of the European Myeloma Network","volume":"24","author":"Ludwig","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/2643-3230.BCD-23-0049","article-title":"IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies","volume":"4","author":"Lancman","year":"2023","journal-title":"Blood Cancer Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1038\/s41591-023-02491-5","article-title":"Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma","volume":"29","author":"Lee","year":"2023","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1182\/blood.2023023557","article-title":"Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma","volume":"144","author":"Firestone","year":"2024","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Guha, A., and Banerjee, S. (2025). Trogocytosis at the crossroad of cancer and immunity: Mechanisms, implications and therapeutic perspectives. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1676945"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"33621","DOI":"10.18632\/oncotarget.26098","article-title":"Trogocytosis represents a novel mechanism of action of daratumumab in multiple myeloma","volume":"9","author":"Krejcik","year":"2018","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e005091","DOI":"10.1136\/jitc-2022-005091","article-title":"Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization","volume":"10","author":"Camviel","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/s41571-022-00689-z","article-title":"Clinical implications of T cell exhaustion for cancer immunotherapy","volume":"19","author":"Chow","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/17474086.2024.2370552","article-title":"T-cell exhaustion in multiple myeloma","volume":"17","author":"Zylka","year":"2024","journal-title":"Expert. Rev. Hematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13045-016-0345-3","article-title":"T cells in multiple myeloma display features of exhaustion and senescence at the tumor site","volume":"9","author":"Thangavadivel","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Du, J., and Shen, X. (2023). Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1157537"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12943-022-01657-y","article-title":"Myeloid-derived suppressor cells: An emerging target for anticancer immunotherapy","volume":"21","author":"Wu","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Racacho, K.J., Shiau, Y.P., Villa, R., Mahri, S., Tang, M., Lin, T.Y., and Li, Y. (2025). The tumor immune microenvironment: Implications for cancer immunotherapy, treatment strategies, and monitoring approaches. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1621812"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Slomp, A., and Peperzak, V. (2018). Role and Regulation of Pro-survival BCL-2 Proteins in Multiple Myeloma. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00533"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10532","DOI":"10.18632\/oncotarget.3300","article-title":"Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells","volume":"6","author":"Lub","year":"2015","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1016\/j.ymthe.2025.04.019","article-title":"Enhanced CAR-T cell function and mitochondrial fitness from earlier unfractionated stem cell product in multiple myeloma","volume":"33","author":"Freeman","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Binder, A.F., Walker, C.J., Mark, T.M., and Baljevic, M. (2023). Impacting T-cell fitness in multiple myeloma: Potential roles for selinexor and XPO1 inhibitors. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1275329"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1182\/blood.2024026212","article-title":"Impact of soluble BCMA and non-T-cell factors on refractoriness to BCMA-targeting T-cell engagers in multiple myeloma","volume":"144","author":"Lee","year":"2024","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41467-021-21177-5","article-title":"Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma","volume":"12","author":"Samur","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3324\/haematol.2020.266841","article-title":"BCMA loss in the epoch of novel immunotherapy for multiple myeloma: From biology to clinical practice","volume":"108","author":"Zhou","year":"2023","journal-title":"Haematologica"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41571-024-00905-y","article-title":"Bispecific and multispecific antibodies in oncology: Opportunities and challenges","volume":"21","author":"Goebeler","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"102240","DOI":"10.1016\/j.ctrv.2021.102240","article-title":"The promise of bispecific antibodies: Clinical applications and challenges","volume":"99","author":"Lim","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Pillarisetti, K., Yang, D., Luistro, L., Yao, J., Smith, M., Vulfson, P., Testa, J., Ponticiello, R., Brodeur, S.R., and Heidrich, B. (2025). Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. Blood.","DOI":"10.1182\/blood.2025030027"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13543776.2024.2423018","article-title":"Trispecific anti-CD3\/BCMA\/CD38 antibodies for multiple myeloma: A patent evaluation of US20240132615","volume":"35","author":"Bandala","year":"2025","journal-title":"Expert. Opin. Ther. Pat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1111\/bjh.19784","article-title":"A CD38\/CD3xCD28 trispecific T-cell engager as a potentially active agent in multiple myeloma patients relapsed and\/or refractory to anti-CD38 monoclonal antibodies","volume":"205","author":"Zabaleta","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s43018-024-00821-1","article-title":"ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells","volume":"5","author":"Hall","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1158\/2767-9764.CRC-23-0434","article-title":"Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies","volume":"4","author":"Keller","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1182\/blood.2019000050","article-title":"gamma-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma","volume":"134","author":"Pont","year":"2019","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S1470-2045(23)00246-2","article-title":"gamma-Secretase inhibitor in combination with BCMA chimeric antigen receptor T-cell immunotherapy for individuals with relapsed or refractory multiple myeloma: A phase 1, first-in-human trial","volume":"24","author":"Cowan","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Chari, A., van de Donk, N., Dholaria, B., Weisel, K.C., Mateos, M.V., Goldschmidt, H., Martin, T.G., Morillo, D., Reece, D., and Rodriguez-Otero, P. (2025). Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood.","DOI":"10.1182\/blood.2025029360"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMoa2406536","article-title":"Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma","volume":"392","author":"Cohen","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e4258276","DOI":"10.1097\/01.HS9.0000975288.42582.76","article-title":"Magnetismm-7: An Open-Label, Multicenter, Randomized Phase 3 Study of Elranatamab Versus Lenalidomide in Post-Transplant Patients with Newly Diagnosed Multiple Myeloma","volume":"7","author":"Manteca","year":"2023","journal-title":"Hemasphere"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1182\/blood-2022-162733","article-title":"MonumenTAL-3: Phase 3 Trial of Talquetamab + Daratumumab \u00b1 Pomalidomide Versus Daratumumab + Pomalidomide + Dexamethasone in Relapsed\/Refractory Multiple Myeloma Following \u22651 Prior Line of Therapy","volume":"140","author":"Moreau","year":"2022","journal-title":"Blood"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/12\/2113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T12:29:51Z","timestamp":1764246591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/12\/2113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":87,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["medicina61122113"],"URL":"https:\/\/doi.org\/10.3390\/medicina61122113","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]}}}