Keywords
Bispecific antibody
Solid tumors
Immunotherapy
Targeted therapy
Submitted : 2026-05-19
Accepted : 2026-06-03
Published : 2026-06-18
Abstract
Background: Although bispecific antibodies (BsAbs) hold promising therapeutic prospects in solid tumors, there is scarce bibliometric analysis on this field. This study aimed to systematically map the research landscape, identify key trends, and highlight future directions for BsAb research in solid tumors. Methods: Literature of BsAb development for solid tumors was retrieved from Web of Science Core Collection published between 2006 and 2025. Publication distribution, research trends and hotspots were analyzed and visualized by VOSviewer, CiteSpace and the R package “bibliometrix”. Results: Overall, we identified 3632 publications stemming from a fast-growing field currently strongly influenced by the United States and China, with Memorial Sloan Kettering Cancer Center and National Cancer Institute the most productive research centers, Front Immunol the most productive journal and J Clin Oncol the most cited. The dominant research topics that appeared from keyword analysis are bispecific antibody, immunotherapy, targeted therapy, non-small cell lung cancer, and EGFR. Conclusion: This study documents the evolution of BsAb research, from basic science to clinical translational research in solid tumors. The research in this field is highly mature at this point, with emphasis on the targeting of specific tumor types and specific antigens. In order to further push forward the frontier, greater international and subfield collaborations, as well as larger-scale clinical trials targeting broader indications, overcoming resistant mechanisms and combination strategies are necessary.
References
Baeuerle PA, Reinhardt C, 2009, Bispecific T-Cell Engaging Antibodies for Cancer Therapy. Cancer Res, 69(12): 4941–4944.
Blair HA, 2025, Zenocutuzumab: First Approval. Drugs, 85(4): 591–597.
Borrelli R, Brussino L, Negrini S, et al., 2025, From Molecular Engineering to Clinical Applications: The Expanding Role of Bispecific Antibodies in Onco-Immunology. Pharmacol Res, 221: 108000.
Nisonoff A, Rivers MM, 1961, Recombination of a Mixture of Univalent Antibody Fragments of Different Specificity. Arch Biochem Biophys, 93: 460–462.
Karbyshev MS, Kalashnikova IV, Dubrovskaya VV, et al., 2025, Trends and Challenges in Bispecific Antibody Production. J Chromatogr A, 1744: 465722.
Fan G, Wang Z, Hao M, et al., 2015, Bispecific Antibodies and Their Applications. J Hematol Oncol, 8: 130–130.
Spiess C, Zhai Q, Carter PJ, 2015, Alternative Molecular Formats and Therapeutic Applications for Bispecific Antibodies. Mol Immunol, 67(2): 95–106.
Kontermann RE, Brinkmann U, 2015, Bispecific Antibodies. Drug Discov Today, 20(7): 838–847.
Madsen AV, Pedersen LE, Kristensen P, et al., 2024, Design and Engineering of Bispecific Antibodies: Insights and Practical Considerations. Front Bioeng Biotechnol, 12: 1352014.
Shui L, Wu D, Yang K, et al., 2025, Bispecific Antibodies: Unleashing a New Era in Oncology Treatment. Mol Cancer, 24(1): 212.
Krishnamurthy A, Jimeno A, 2018, Bispecific Antibodies for Cancer Therapy: A Review. Pharmacol Ther, 185: 122–134.
Brinkmann U, Kontermann RE, 2017, The Making of Bispecific Antibodies. MAbs, 2017, 9(2): 182–212.
Shastri T, Trabolsi A, Arumov A, et al., 2025, Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline. BioDrugs, 39(5): 793–814.
Shouse G, 2025, Bispecific Antibodies for the Treatment of Hematologic Malignancies: The Magic Is T-Cell Redirection. Blood Rev, 69: 101251.
Sanford M, 2015, Blinatumomab: First Global Approval. Drugs, 75(3): 321–327.
Wu Y, Yi M, Zhu S, et al., 2021, Recent Advances and Challenges of Bispecific Antibodies in Solid Tumors. Exp Hematol Oncol, 10(1): 56.
Dhillon S, 2024, Ivonescimab: First Approval. Drugs, 84(9): 1135–1142.
Dhillon S, 2024, Tarlatamab: First Approval. Drugs, 84(8): 995–1003.
Keam SJ, 2025, Zanidatamab: First Approval. Drugs, 85(5): 707–714.
van Eck NJ, Waltman L, 2017, Citation-Based Clustering of Publications Using CitNetExplorer and VOSviewer. Scientometrics, 111(2): 1053–1070.
Chen C, 2017, Science Mapping: A Systematic Review of the Literature. Journal of Data and Information Science, 2(2): 1–40.
Labrijn AF, Janmaat ML, Reichert JM, et al., 2019, Bispecific Antibodies: A Mechanistic Review of the Pipeline. Nat Rev Drug Discov, 18(8): 585–608.
Ridgway JB, Presta LG, Carter P, 1996, Knobs-into-Holes Engineering of Antibody CH3 Domains for Heavy Chain Heterodimerization. Protein Eng, 9(7): 617–621.
Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71(3): 209–249.
Nathan P, Hassel JC, Rutkowski P, et al., 2021, Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med, 385(13): 1196–1206.
Park K, Haura EB, Leighl NB, et al., 2021, Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol, 39(30): 3391–3402.
No Authors Listed, 2021, Congress Approves Increase in Cancer Funding. Cancer Discov, 11(3): 524–524.
Merchant AM, Zhu Z, Yuan JQ, et al., 1998, An Efficient Route to Human Bispecific IgG. Nat Biotechnol, 16(7): 677–681.
Kroesen BJ, Buter J, Sleijfer DT, et al., 1994, Phase I Study of Intravenously Applied Bispecific Antibody in Renal Cell Cancer Patients Receiving Subcutaneous Interleukin 2. Br J Cancer, 70(4): 652–661.
Joshi KK, Phung W, Han G, et al., 2019, Elucidating Heavy/Light Chain Pairing Preferences to Facilitate the Assembly of Bispecific IgG in Single Cells. MAbs, 11(7): 1254–1265.
Yang Z, Jiang L, 2014, Building Clinical Research Capacity in China: The National Clinical Research Centres. Lancet, 383(9913): 200–201.
Zhou P, Glänzel W, 2010, In-Depth Analysis on China’s International Cooperation in Science. Scientometrics, 2010, 82(3): 597–612. [26] Nisonoff A, Rivers MM, 1961, Recombination of a Mixture of Univalent Antibody Fragments of Different Specificity. Arch Biochem Biophys, 93: 460–462.
Izarn F, Henry J, Besle S, et al., 2025, Globalization of Clinical Trials in Oncology: A Worldwide Quantitative Analysis. ESMO Open, 10(1): 104086.
Gera N, 2022, The Evolution of Bispecific Antibodies. Expert Opin Biol Ther, 22(8): 945–949.
Zhang Z, Luo F, Cao J, et al., 2021, Anticancer Bispecific Antibody R&D Advances: A Study Focusing on Research Trend Worldwide and in China. J Hematol Oncol, 14(1): 124.
Chen C, 2006, CiteSpace II: Detecting and Visualizing Emerging Trends and Transient Patterns in Scientific Literature. Journal of the American Society for Information Science and Technology, 57(3): 359–377.
Zhou C, Tang KJ, Cho BC, et al., 2023, Amivantamab Plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. N Engl J Med, 389(22): 2039–2051.
Yang JC, Lu S, Hayashi H, et al., 2025, Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC. N Engl J Med, 393(17): 1681–1693.
Wu F, Gao J, Kang J, et al., 2022, Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002–2021). Front Immunol, 13: 939433.
Burges A, Wimberger P, Kümper C, et al., 2007, Effective Relief of Malignant Ascites in Patients with Advanced Ovarian Cancer by a Trifunctional Anti-EpCAM x Anti-CD3 Antibody: A Phase I/II Study. Clin Cancer Res, 13(13): 3899–3905.
Lewis SM, Wu X, Pustilnik A, et al., 2014, Generation of Bispecific IgG Antibodies by Structure-Based Design of an Orthogonal Fab Interface. Nat Biotechnol, 32(2): 191–198.
Spiess C, Merchant M, Huang A, et al., 2013, Bispecific Antibodies with Natural Architecture Produced by Co-Culture of Bacteria Expressing Two Distinct Half-Antibodies. Nat Biotechnol, 31(8): 753–758.
Verkleij CPM, Broekmans MEC, van Duin M, et al., 2021, Preclinical Activity and Determinants of Response of the GPRC5DxCD3 Bispecific Antibody Talquetamab in Multiple Myeloma. Blood Adv, 5(8): 2196–2215.
Pang X, Huang Z, Zhong T, et al., 2023, Cadonilimab, a Tetravalent PD-1/CTLA-4 Bispecific Antibody with Trans-Binding and Enhanced Target Binding Avidity. MAbs, 15(1): 2180794.
Moores SL, Chiu ML, Bushey BS, et al., 2016, A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res, 76(13): 3942–3953.
Zhang J, Ji D, Cai L, et al., 2022, First-in-Human HER2-Targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer: Results from a Phase I Study. Clin Cancer Res, 28(4): 618–628.
Xu J, Ying J, Liu R, et al., 2023, KN026 (Anti-HER2 Bispecific Antibody) in Patients with Previously Treated, Advanced HER2-Expressing Gastric or Gastroesophageal Junction Cancer. Eur J Cancer, 178: 1–12.
Reusch U, Sundaram M, Davol PA, et al., 2006, Anti-CD3 x Anti-Epidermal Growth Factor Receptor (EGFR) Bispecific Antibody Redirects T-Cell Cytolytic Activity to EGFR-Positive Cancers in Vitro and in an Animal Model. Clin Cancer Res, 12(1): 183–190.
Vincent KJ, Zurini M, 2012, Current Strategies in Antibody Engineering: Fc Engineering and pH-Dependent Antigen Binding, Bispecific Antibodies and Antibody Drug Conjugates. Biotechnol J, 7(12): 1444–1450.