[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-354344-105":59,"doc-detail-354344-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","a-new-paradigm-of-bispecific-antibodies-in-clinical-management-of-gastrointestinal-cancers","A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers","","Gastrointestinal (GI) cancers impose a major global health burden, with high incidence, poor prognosis, and limited benefit from monotherapies. Bispecific antibodies (BsAbs) offer a dual-targeting paradigm that combines tumor-associated antigen recognition with immune effector recruitment to strengthen antitumor activity. This review surveys recent BsAb-based immunotherapy progress across colorectal, gastric, pancreatic, biliary tract, esophageal, and liver cancers, summarizing molecular targets and representative clinical candidates, while addressing tumor microenvironment modulation, resistance, and combination approaches. Key challenges include CRS, on-target/off-tumor toxicity, heterogeneity-driven resistance, and TME constraints, alongside optimization strategies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-new-paradigm-of-bispecific-antibodies-in-clinical-management-of-gastrointestinal-cancers/354344/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-new-paradigm-of-bispecific-antibodies-in-clinical-management-of-gastrointestinal-cancers/354344.png","ImageObject",300,407,{"name":92,"@type":93},"4398046744996","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are bispecific antibodies considered a new therapeutic paradigm for gastrointestinal cancers?","Question",{"text":112,"@type":113},"BsAbs enable dual targeting by binding tumor-associated antigens while recruiting immune effector mechanisms. This physical bridging strengthens antitumor immune surveillance and can address limitations seen with monotherapies.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which gastrointestinal cancer types does the review cover?",{"text":117,"@type":113},"The review surveys progress across major GI malignancies including colorectal, gastric, pancreatic, biliary tract, esophageal, and liver cancers.",{"name":119,"@type":110,"acceptedAnswer":120},"What major challenges limit BsAb efficacy and how are they addressed?",{"text":121,"@type":113},"Key issues include cytokine release syndrome, on-target/off-tumor toxicity, and resistance driven by tumor heterogeneity and the tumor microenvironment. Proposed mitigation strategies include affinity-tuned or conditional activation designs, biomarker-driven patient stratification, combination therapies, and AI-guided optimization.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},354344,1790177322,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":66,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},4398046744996,"| [http://doi.org/10.32604/or.2026.078825](http://doi.org/10.32604/or.2026.078825) |  |\n| --- | --- |\n|  | |\n| REVIEW\u003Cbr>A New Paradigm ofBispecific Antibodies in Clinical Management of Gastrointestinal Cancers\u003Cbr>Huimin Zhao 1,\\# , Xiuran Wang2,\\# , Zhimeng Fan3 , Ai Sun4 , Changhua Zhang 1, *\u003Cbr>and Chunhui Sun 1, *\u003Cbr>1Digestive Diseases Center, Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China\u003Cbr>2 College of Laboratory Animal Science, Shandong First Medical University, Jinan, China\u003Cbr>3Division of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden\u003Cbr>4Breeding and Biotechnology Research Laboratory, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China\u003Cbr>*Corresponding Authors: Changhua Zhang. Email: [zhchangh@mail.sysu.edu.cn](zhchangh@mail.sysu.edu.cn); Chunhui Sun. Email: [sunchh6@mail.sysu.edu.cn](sunchh6@mail.sysu.edu.cn)\u003Cbr>[\\#](# These authors contributed equally to this work)[ These authors contributed equally to this work](# These authors contributed equally to this work)\u003Cbr>Received: 08 January 2026; Accepted: 25 March 2026; Published: 16 June 2026\u003Cbr>ABSTRACT: Gastrointestinal (GI) cancers represent a significant global health burden, characterized by high incidence, poor prognosis, and limited response to monotherapies. The advent ofbispecific antibodies (BsAbs) has introduced a novel therapeutic paradigm, enabling dual targeting of tumor-associated antigens and immune effectorsto enhance antitumor immunity. This review provides a comprehensive overview of recent advances in bsAb-based immunotherapy across major GI malignancies, including colorectal, gastric, pancreatic, biliary tract, esophageal, and liver cancers. We summarize key molecular targets and highlight representative clinical candidates such as CEA-TCBand RG7802 . The discussion extends to innovative strategies involving BsAbs in modulating the immunosuppressive tumor microenvironment and overcoming resistance mechanisms. Furthermore, we explore promising combination therapies involving BsAbs with chemotherapy and immune checkpoint inhibitors (ICIs) . The role of artificial intelligence in target prediction and structure optimization is also examined, alongside the potential of personalized immune strategies. Despite promising therapeutic potential, BsAbs face challenges including cytokine release syndrome (CRS), on-target/off-tumor toxicity, tumor heterogeneity-driven resistance, and tumor microenvironment (TME) . Current strategies to improve therapeutic index encompass affinity-tuned designs, conditional activation mechanisms, biomarker-driven patient stratification, combination therapies, and artificial intelligence (AI)-guided optimization, warranting continued interdisciplinary research efforts. We conclude by outlining future research directions and emphasizing the importance of interdisciplinary, multicenter collaborations to accelerate clinical translation and maximize the therapeutic potential of BsAbs in GI oncology. In summary, the aim of this study is to critically evaluate the current landscape of BsAb-based immunotherapy in gastrointestinal cancers, synthesizing emerging molecular targets, evaluating clinical trial outcomes, identifying key challenges limiting therapeutic efficacy, and proposing evidence-based strategies to optimize future BsAb development.\u003Cbr>KEYWORDS: Gastrointestinal cancers; bispecific antibodies; molecular targets; tumor-associated antigen; immunotherapy |  |\n\n1 Introduction  \nGastrointestinal (GI) cancers represent a biologically and clinically heterogeneous group of malignancies, including gastric, colorectal, esophageal, pancreatic, and rare neuroendocrine tumors, remain a leading cause of global cancer mortality, with increasing incidence in younger populations [1–4] .  \nCopyright © 2026 The Authors. Published by Tech Science Press. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits","cbCaicps79qcdG85","https://ap.wps.com/l/cbCaicps79qcdG85","pdf",1871451,41,"English","# Introduction\n## Rationale for BsAbs in GI malignancies\n# Bispecific antibody mechanisms\n## Immune cell redirection and target bridging\n## Antitumor effects via cytotoxic pathways\n# Emerging clinical landscape\n## Representative molecular targets and candidates\n# Strategies to improve therapeutic outcomes\n## Overcoming resistance and modulating TME\n## Combination therapies with chemotherapy and ICIs\n## AI-guided target prediction and optimization\n# Safety challenges and mitigation approaches\n## Cytokine release syndrome and toxicity management\n# Future directions","[{\"question\":\"Why are bispecific antibodies considered a new therapeutic paradigm for gastrointestinal cancers?\",\"answer\":\"BsAbs enable dual targeting by binding tumor-associated antigens while recruiting immune effector mechanisms. This physical bridging strengthens antitumor immune surveillance and can address limitations seen with monotherapies.\"},{\"question\":\"Which gastrointestinal cancer types does the review cover?\",\"answer\":\"The review surveys progress across major GI malignancies including colorectal, gastric, pancreatic, biliary tract, esophageal, and liver cancers.\"},{\"question\":\"What major challenges limit BsAb efficacy and how are they addressed?\",\"answer\":\"Key issues include cytokine release syndrome, on-target/off-tumor toxicity, and resistance driven by tumor heterogeneity and the tumor microenvironment. Proposed mitigation strategies include affinity-tuned or conditional activation designs, biomarker-driven patient stratification, combination therapies, and AI-guided optimization.\"}]","A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers | PDF",1790110207,103]