{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:34:11Z","timestamp":1787567651656,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, with five-year survival below 5% for metastatic small cell lung cancer (SCLC) and below 10% for metastatic non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors have improved outcomes, but primary and acquired resistance, driven by tumor microenvironment immunosuppression, antigen heterogeneity, and T-cell exhaustion, leaves a substantial unmet need. T-cell engagers (TCEs), bispecific antibodies that redirect cytotoxic T-cells to tumor cells independent of MHC-I-restricted antigen presentation, offer a mechanistically distinct approach. Methods: We conducted a structured narrative review, without formal PRISMA methodology or meta-analytic pooling, of PubMed, Embase, and ClinicalTrials.gov through June 2026, supplemented by conference abstracts from ASCO, ESMO, AACR, and ATS, covering clinical, translational, and preclinical evidence for TCEs across established and emerging targets in thoracic malignancy. Results: Tarlatamab, a DLL3\/CD3 bispecific TCE, received full FDA approval in November 2025 based on DeLLphi-304 data showing a median overall survival benefit of 13.6 versus 8.3 months over chemotherapy (HR 0.60; p &lt; 0.001), establishing proof-of-concept for the TCE platform in lung cancer and NCCN Category 1 status in ES-SCLC. Beyond DLL3, an expanding pipeline of targets, including Claudin-18.2, TROP-2, FOLR1, CD70, and HER2, is under active TCE development; several of these antigens have independently validated tumor-selective expression through approved or late-stage antibody-drug conjugates (ADCs), providing target-level clinical de-risking for TCE development, though the two modalities have distinct requirements for antigen density and internalization that must be independently validated. Novel tri-specific constructs incorporating costimulatory domains and combination strategies with checkpoint inhibitors are in early clinical development. Conclusions: Tarlatamab approval validates the TCE platform in lung cancer, but overcoming TME-mediated resistance, antigen heterogeneity, and class-specific toxicities including cytokine release syndrome remains the central challenge. Rational TCE design, incorporating costimulatory signaling, antigen selection informed by parallel ADC validation data, and evidence-based combination strategies, offers the most credible path toward expanding this platform\u2019s impact in metastatic lung cancer.<\/jats:p>","DOI":"10.3390\/cancers18172725","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["T-Cell Engagers in Lung Cancer: A Comprehensive Literature Review from Tarlatamab Approval to Next-Generation Strategies"],"prefix":"10.3390","volume":"18","author":[{"given":"Adnan","family":"Saydawi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, McLaren Oakland Hospital, Michigan State University, Pontiac, MI 48342, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Madanieh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4853-7272","authenticated-orcid":false,"given":"Stephanie L.","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angad","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sweta","family":"Modha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beyan","family":"El Emin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqar","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bsher","family":"Almaalouli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida, Lake Nona, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0775-2680","authenticated-orcid":false,"given":"Mohamed","family":"Shanshal","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1056\/NEJMra0802714","article-title":"Lung cancer","volume":"359","author":"Herbst","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","unstructured":"National Cancer Institute (2026, June 01). SEER*Explorer: An Interactive Website for SEER Cancer Statistics. Surveillance Research Program, National Cancer Institute, Available online: https:\/\/seer.cancer.gov\/explorer\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40364-020-00212-5","article-title":"Resistance to PD-1\/PD-L1 blockade cancer immunotherapy: Mechanisms, predictive factors, and future perspectives","volume":"8","author":"Sun","year":"2020","journal-title":"Biomark. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhou, X., Ni, Y., Liang, X., Lin, Y., An, B., He, X., and Zhao, X. (2022). Mechanisms of tumor resistance to immune checkpoint blockade and combination strategies to overcome resistance. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.915094"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2017.04.004","article-title":"CAR T-cell therapy for lung cancer and malignant pleural mesothelioma","volume":"187","author":"Zeltsman","year":"2017","journal-title":"Transl. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chocarro, L., Arasanz, H., Fernandez-Rubio, L., Blanco, E., Echaide, M., Bocanegra, A., Teijeira, L., Garnica, M., Morilla, I., and Martinez-Aguillo, M. (2022). CAR-T Cells for the Treatment of Lung Cancer. Life, 12.","DOI":"10.3390\/life12040561"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ijc.70093","article-title":"Advances in CAR-T therapy for small cell lung cancer","volume":"158","author":"Zhang","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"TPS8576","DOI":"10.1200\/JCO.2019.37.15_suppl.TPS8576","article-title":"Phase 1 study of AMG 119, a chimeric antigen receptor (CAR) T cell therapy targeting DLL3, in patients with relapsed\/refractory small cell lung cancer (SCLC)","volume":"37","author":"Byers","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12935-024-03315-3","article-title":"Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors","volume":"24","author":"Chen","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/mt.2010.24","article-title":"Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2","volume":"18","author":"Morgan","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1158\/2159-8290.CD-24-0645","article-title":"Lung Cancer Adoptive Cell Therapy: Inspiring TIL ACT Comes Center Stage","volume":"14","author":"Lotze","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eadf3700","DOI":"10.1126\/sciadv.adf3700","article-title":"TCR-engineered T cell therapy in solid tumors: State of the art and perspectives","volume":"9","author":"Baulu","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/imr.13233","article-title":"Challenges and solutions for therapeutic TCR-based agents","volume":"320","author":"Malviya","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shanshal, M., Caimi, P.F., Adjei, A.A., and Ma, W.W. (2023). T-Cell Engagers in Solid Cancers-Current Landscape and Future Directions. Cancers, 15.","DOI":"10.3390\/cancers15102824"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMoa2307980","article-title":"Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer","volume":"389","author":"Ahn","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1056\/NEJMoa2502099","article-title":"Tarlatamab in small-cell lung cancer after platinum-based chemotherapy","volume":"393","author":"Mountzios","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41423-020-0417-8","article-title":"Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics","volume":"17","author":"Li","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14397","DOI":"10.1038\/s41598-021-93842-0","article-title":"Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning","volume":"11","author":"Haber","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2584374","DOI":"10.1080\/19420862.2025.2584374","article-title":"Optimizing efficacy and safety of T cell bispecific antibodies: The interdependence of CD3 and tumor antigen binder affinities in FOLR1 and CEACAM5 2+1 TCBs","volume":"17","author":"Abdelmotaleb","year":"2025","journal-title":"mAbs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1158\/1535-7163.MCT-24-0846","article-title":"Optimization of a novel 2+2 BCMA x CD3 bispecific antibody for minimized cytokine release and potent efficacy","volume":"24","author":"Wu","year":"2025","journal-title":"Mol. Cancer Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaax1315","DOI":"10.1126\/scitranslmed.aax1315","article-title":"Interdomain spacing and spatial configuration drive the potency of IgG-[L]-scFv T cell bispecific antibodies","volume":"12","author":"Santich","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41577-021-00547-6","article-title":"Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy","volume":"22","author":"Morris","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e009563","DOI":"10.1136\/jitc-2024-009563","article-title":"SAIL66, a next generation CLDN6-targeting T-cell engager, demonstrates potent antitumor efficacy through dual binding to CD3\/CD137","volume":"12","author":"Kiefer","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2510829122","DOI":"10.1073\/pnas.2510829122","article-title":"EVOLVE platform, a trispecific T cell engager with integrated CD2 costimulation, for the treatment of solid and hematologic tumors","volume":"122","author":"Sergeeva","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s40259-025-00752-y","article-title":"Conditionally activatable antibody platforms: Mechanisms, modalities, and clinical translation potential","volume":"40","author":"Kim","year":"2026","journal-title":"BioDrugs"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1852900","DOI":"10.1080\/19420862.2020.1792130","article-title":"COBRA: A highly potent conditionally active T cell engager engineered for the treatment of solid tumors","volume":"12","author":"Panchal","year":"2020","journal-title":"mAbs"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1158\/1078-0432.CCR-25-2287","article-title":"FDA Approval Summary: Tarlatamab for the treatment of extensive stage small cell lung cancer","volume":"32","author":"Barone","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_30","unstructured":"US Food and Drug Administration (2026, July 30). FDA Grants Traditional Approval to Tarlatamab-Dlle for Extensive Stage Small Cell Lung Cancer, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"LBA8008","DOI":"10.1200\/JCO.2025.43.17_suppl.LBA8008","article-title":"Tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304","volume":"43","author":"Rudin","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S2213-2600(22)00309-5","article-title":"Combination lurbinectedin and doxorubicin versus physician\u2019s choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): A multicentre, randomised, open-label, phase 3 trial","volume":"11","author":"Aix","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_33","unstructured":"Jazz Pharmaceuticals (2026, August 04). Jazz Pharmaceuticals Provides Update on Zepzelca (Lurbinectedin) Phase 3 LAGOON Trial in Second-Line Small Cell Lung Cancer. Press Release, 12 June 2026. Available online: https:\/\/www.prnewswire.com\/news-releases\/jazz-pharmaceuticals-provides-update-on-zepzelca-lurbinectedin-phase-3-lagoon-trial-in-second-line-small-cell-lung-cancer-302798651.html."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109465","DOI":"10.1016\/j.lungcan.2026.109465","article-title":"Comparative efficacy of tarlatamab and second-line therapies in extensive-stage small cell lung cancer: A network meta-analysis","volume":"217","author":"Wang","year":"2026","journal-title":"Lung Cancer"},{"key":"ref_35","first-page":"e260002","article-title":"NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2026","volume":"24","author":"Ganti","year":"2026","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8006","DOI":"10.1200\/JCO.2026.44.16_suppl.8006","article-title":"Intracranial efficacy of tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): DeLLphi-304 phase 3 post hoc analysis","volume":"44","author":"Mountzios","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/S1470-2045(25)00480-2","article-title":"Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): A multicentre, non-randomised, phase 1b study","volume":"26","author":"Paulson","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1200\/JCO-25-00363","article-title":"Phase I dose-escalation results for the delta-like ligand 3\/CD3 IgG-like T-cell engager obrixtamig (BI 764532) in patients with delta-like ligand 3+ small cell lung cancer or neuroendocrine carcinomas","volume":"43","author":"Wermke","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8094","DOI":"10.1200\/JCO.2025.43.16_suppl.8094","article-title":"DAREON-9, a phase Ib study of obrixtamig plus topotecan in patients with advanced small cell lung cancer (SCLC): Interim analysis results","volume":"43","author":"Wermke","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1056\/NEJMoa2304753","article-title":"Three-year overall survival with tebentafusp in metastatic uveal melanoma","volume":"389","author":"Hassel","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1158\/2159-8290.CD-23-0964","article-title":"Xaluritamig, a STEAP1 x CD3 XmAb 2+1 immune therapy for metastatic castration-resistant prostate cancer","volume":"14","author":"Kelly","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s00262-024-03673-x","article-title":"DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy","volume":"73","author":"Ma","year":"2024","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.immuni.2024.04.021","article-title":"Expression of the membrane tetraspanin claudin 18 on cancer cells promotes T lymphocyte infiltration and antitumor immunity in pancreatic cancer","volume":"57","author":"Dusi","year":"2024","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s41568-019-0179-8","article-title":"Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy","volume":"19","author":"Skoulidis","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","first-page":"100943","article-title":"The landscape of CEACAM5 expression by immunohistochemistry in NSCLC","volume":"7","author":"Hsu","year":"2025","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1038\/s41467-024-48479-8","article-title":"CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: Results of two multi-institutional Phase 1 trials","volume":"15","author":"Segal","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"188902","DOI":"10.1016\/j.bbcan.2023.188902","article-title":"Targeting Trop-2 in cancer: Recent research progress and clinical application","volume":"1878","author":"Qiu","year":"2023","journal-title":"Biochim. Biophys. Acta-Rev. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"501","DOI":"10.21037\/atm-22-621","article-title":"The anti-Trop-2 antibody-drug conjugate Sacituzumab Govitecan-effectiveness, pitfalls and promises","volume":"10","author":"Guerra","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.4161\/cbt.26341","article-title":"Chemotherapy agents-induced immunoresistance in lung cancer cells could be reversed by trop-2 inhibition in vitro and in vivo by interaction with MAPK signaling pathway","volume":"14","author":"Wang","year":"2013","journal-title":"Cancer Biol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa2112431","article-title":"Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","volume":"386","author":"Li","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"52553","DOI":"10.18632\/oncotarget.9651","article-title":"Targeting folate receptor alpha for cancer treatment","volume":"7","author":"Cheung","year":"2016","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"TPS3157","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS3157","article-title":"Phase 1\/2 study of PRO1184, a novel folate receptor alpha-directed antibody-drug conjugate, in patients with locally advanced and\/or metastatic solid tumors","volume":"41","author":"Call","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2192100","DOI":"10.1080\/2162402X.2023.2192100","article-title":"Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer","volume":"12","author":"Flieswasser","year":"2023","journal-title":"OncoImmunology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13462","DOI":"10.18632\/oncotarget.3880","article-title":"Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer","volume":"6","author":"Jacobs","year":"2015","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ning, J., Jiang, S., Li, X., Zhang, Y., Liu, Y., Chen, X., Zhao, Y., Xu, R., Wang, L., and Li, W. (2021). GPC3 affects the prognosis of lung adenocarcinoma and lung squamous cell carcinoma. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01549-9"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.molmed.2014.02.007","article-title":"MUC1: A multifaceted oncoprotein with a key role in cancer progression","volume":"20","author":"Nath","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S385","DOI":"10.1016\/j.annonc.2024.08.344","article-title":"Evaluation of MUC1-C\/CD3 biparatopic-bispecific (BPBS) T cell engager as an immunotherapeutic agent for the treatment of MUC1-expressing metastatic breast cancer (mBC)","volume":"35","author":"Jasuja","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e1091555","DOI":"10.1080\/2162402X.2015.1091555","article-title":"Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the oncofetal protein claudin 6","volume":"5","author":"Stadler","year":"2016","journal-title":"OncoImmunology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"104755","DOI":"10.1016\/j.yexmp.2022.104755","article-title":"B7-H4 expression promotes non-small cell lung cancer progression via AMPK\/mTOR signaling","volume":"125","author":"Li","year":"2022","journal-title":"Exp. Mol. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1200\/JCO.2023.41.16_suppl.2534","article-title":"Clinical development of the bispecific PSMAxCD3 antibody CC-1","volume":"41","author":"Hackenbruch","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wang, H.L., Wang, S.S., Song, W.H., Pan, Y., Yu, L., Sillanp\u00e4\u00e4, A., Kuruma, H., Zhang, Y., Liu, Y., and Chen, X. (2015). Expression of Prostate-Specific Membrane Antigen in Lung Cancer Cells and Tumor Neovasculature Endothelial Cells and Its Clinical Significance. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125924"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1158\/2159-8290.CD-25-1483","article-title":"Circulating tumor cells predict response to the DLL3-targeting bispecific antibody tarlatamab","volume":"16","author":"Mishra","year":"2026","journal-title":"Cancer Discov."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"114075","DOI":"10.1016\/j.ejca.2024.114075","article-title":"Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review","volume":"205","author":"Gerard","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Godel","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3978","DOI":"10.1200\/JCO.21.01992","article-title":"Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline","volume":"39","author":"Santomasso","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"116686","DOI":"10.1016\/j.ejca.2026.116686","article-title":"Risk factors for CRS and ICANS with tarlatamab in small cell lung cancer and associated efficacy outcomes: Insights from clinical practice","volume":"238","author":"Blocker","year":"2026","journal-title":"Eur. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1038\/s41467-023-40850-5","article-title":"Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors","volume":"14","author":"Xiao","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ymeth.2018.10.026","article-title":"Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety","volume":"154","author":"Ellerman","year":"2019","journal-title":"Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/s41467-021-21445-4","article-title":"Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation","volume":"12","author":"Arenas","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41571-018-0142-8","article-title":"Cancer immunoediting and resistance to T cell-based immunotherapy","volume":"16","author":"Teng","year":"2019","journal-title":"Nat. Rev. Clin. 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