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  • Development and Immunological Application of Bispecific Antibodies in the Treatment of Gastric Cancer

  • Nadia Keivani,1 Elham Kamalkazemi,2 Roya Herizchighadim,3 Elham Abbasi,4 Masoumeh Amanidolama,5 Effat Alizadeh,6,*
    1. Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran
    2. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    3. Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    4. Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    5. Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    6. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran


  • Introduction: Gastric cancer (GC) is one of the leading causes of death related to cancer worldwide. Despite recent advances in GC treatment, it still faces challenges such as poor diagnosis, tumor heterogeneity, resistance to single-targeted antibody-based therapies (e.g., trastuzumab), and the relative inefficiency of the immune system in the tumoral environment. In recent years, bispecific antibodies (bsAbs) have emerged as a novel strategy in immunotherapy; these engineered molecules can simultaneously target two distinct antigens, typically a tumor surface marker and an immune-activating molecule, thereby directing immune cells to cancer cells. BsAbs can induce apoptosis, pyroptosis, and the activation of macrophages and dendritic cells.
  • Methods: In this narrative review, data from seven advanced dual-target antibodies in gastric cancer, based on preclinical reports and early clinical studies (2019 to 2024), were collected and analyzed. In this regard, we used the terms "gastric cancer," "bispecific antibodies," and "immunotherapy." We searched the PubMed and Google Scholar databases to retrieve relevant articles.
  • Results: The results showed that the dual-targeting antibody B7-H3×CD3, with an IgG-like structure, induced T cell depletion and specific cytotoxicity, significantly reducing tumor growth in the gastric cancer model. The IBI315 (PD-1/HER2) antibody inhibited the PD-1 immunosuppressive pathway and enhanced the antitumor response in HER2-positive cells. Also, the dual CD40 × HER2 bsAb showed 2.3-fold greater cytotoxicity than single-target antibodies in cells co-expressing both markers.
  • Conclusion: These findings revealed the potential efficacy of dual-targeted antibodies as innovative and multifunctional tools in gastric cancer immunotherapy.
  • Keywords: Gastric cancer, Bispecific antibodies, Immunotherapy

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