Ivonescimab Injection can simultaneously bind to Vascular Endothelial Growth Factor-A (VEGF-A) and Programmed Death-1 (PD-1), competitively blocking the interaction between these two targets and their ligands, thereby enhancing anti-tumor activity. Studies have shown that during treatment, Ivonescimab Injection can synergistically exert the dual anti-tumor effects of "immunotherapy + anti-angiogenesis", demonstrating characteristics of broad-spectrum anti-tumor activity and rapid control of tumor growth. Its approval for marketing fills the clinical gap of bispecific immunotherapeutic drugs in the global lung cancer field.

        Bispecific Nanobodies are composed of two single-chain antibody fragments connected via tandem linkage, V-shaped structure, IgG-like structure, or other formats. Each single-chain antibody fragment has affinity for a different target, making bispecific nanobodies a type of nanobody with dual binding capabilities. They possess higher specificity, better targeting, and lower off-target toxicity, and can be used in the treatment of various diseases, including cancer, autoimmune diseases, and infectious diseases [1].

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        Bispecific nanobodies can simultaneously target two antigens on the surface of tumor cells, thereby increasing the local concentration of the drug and reducing damage to normal cells, bringing new hope to cancer therapy. Research has shown that the bispecific antibody constructed by combining the anti-carcinoembryonic antigen (CEA) nanobody and the anti-CD16 nanobody exhibits a strong ability to mediate Natural Killer (NK) cells in killing CEA-positive cells [2].

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        In addition to their application in cancer therapy, bispecific nanobodies also show great potential in the fields of autoimmune diseases and infectious diseases. For example, Strokappe et al. connected the Variable Domain of Heavy-chain only Antibody (VHH) targeting the non-CD4 binding site (non-CD4bs) epitope (2E7) with the VHH targeting the CD4bs epitope (J3/3E3), and constructed them into an adenoviral vector using gene editing technology, thereby developing a bispecific nanobody against Human Immunodeficiency Virus Type 1 (HIV-1). Compared with the equimolar mixture of specific VHHs, the virus-neutralizing potency of this bispecific nanobody was increased by 1,400 times [3].

        Yang constructed a bispecific nanobody named ABA by fusing multiple anti-toxin VHHs. This bispecific nanobody can simultaneously target the TcdA and TcdB targets in Clostridioides difficile infection (CDI) toxins. Its neutralizing activity was verified in both in vitro and in vivo experiments, and it effectively alleviated the symptoms of CDI in mice [4].

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        Bispecific nanobodies have shown tremendous potential and prospects in cancer therapy and other disease fields. We believe that with the unremitting efforts of scientists, bispecific nanobodies will surely become a powerful tool in the field of medical therapy, bringing more hope and possibilities to human health.

        NBLST focuses on the development, modification, and application of nanobodies. It can provide you with diversified customized nanobody services and create a one-stop service platform for your scientific research projects.

参考文献：
[1]原博，王杰文，康广博，黄鹤.双特异性纳米抗体的研究进展及其应用[J].中国生物工程杂志，2021，41(3):78-88.
[2]DONG B，ZHOU C，HE P，et al.A novel bispecific antibody，BiSS，with potent anti-cancer activities[J].Cancer Biol Ther，2016，17(4):364-370.
[3]Strokappe N M，Hock M，Rutten L，et al.Super potent bispecific llama VHH antibodies neutralize HIV via a combination of gp41 and gp120 epitopes.Antibodies，2019，8(2):38.
[4]Yang Z Y，Schmidt D，Liu W L，et al.A novel multivalent，single-domain antibody targeting TcdA and TcdB prevents fulminant Clostridium difficile infection in mice.The Journal of Infectious Diseases，2014，210(6):964-972.