[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-356624-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-356624-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","immunotherapy-for-pediatric-solid-tumors-overcoming-biological-barriers-through-rational-multimodal-combinations","Immunotherapy for pediatric solid tumors - overcoming biological barriers through rational multimodal combinations","","Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, with biological features that blunt immunotherapy progress seen in adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and highly immunosuppressive tumor microenvironments undermine T cell-dependent mechanisms. The field is shifting through anti-GD2 monoclonal antibodies in high-risk neuroblastoma, next-generation antibody-drug conjugates and bispecific engagers, and CAR T approaches addressing infiltration, persistence, and antigen escape. Checkpoint inhibitors show durable activity in defined molecular subsets, while oncolytic virotherapy, NK cell engagers, and neoantigen vaccines aim to convert immune-cold tumors for combination-tailored responses.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/immunotherapy-for-pediatric-solid-tumors-overcoming-biological-barriers-through-rational-multimodal-combinations/356624/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/immunotherapy-for-pediatric-solid-tumors-overcoming-biological-barriers-through-rational-multimodal-combinations/356624.png","ImageObject",300,407,{"name":42,"@type":43},"Maya Linwood","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are current immunotherapies less effective in pediatric solid tumors?","Question",{"text":63,"@type":64},"Most pediatric solid tumors are immune-cold, featuring exceptionally low tumor mutational burden and sparse neoantigen landscapes, which reduces T cell priming. They also have profoundly immunosuppressive tumor microenvironments that blunt effector trafficking, priming, and persistence.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do antibody-based therapies improve outcomes in pediatric neuroblastoma?",{"text":68,"@type":64},"Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma. Next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 broaden antibody-based strategies across pediatric tumor histologies.",{"name":70,"@type":61,"acceptedAnswer":71},"Which emerging platforms aim to overcome barriers beyond checkpoint blockade?",{"text":72,"@type":64},"Emerging approaches include CAR T cell therapies with engineering strategies (e.g., cytokine armoring, bispecific constructs, locoregional delivery), oncolytic virotherapy, NK cell engagers, and neoantigen vaccines. These aim to address infiltration, persistence, antigen escape, and the conversion of immune-cold tumors into treatment-responsive phenotypes.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},356624,1790472318,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":118,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":104},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Cancer Immunology, Immunotherapy (2026) 75:146  \n[https://doi.org/10.1007/s00262-026-04384-1](https://doi.org/10.1007/s00262-026-04384-1)  \nImmunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations  \nMahsa Fatahichegeni1 · Mohammad Amin Ansarian1 · Mi Xiao1 · Wenjuan Gao1 · Ruiming Shi1  \nReceived: 7 February 2026 / Accepted: 25 March 2026 © The Author(s) 2026  \nAbstract  \nPediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generation antibody–drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 are extending the reach of antibody-based approaches across pediatric histologies. CAR T cell therapies have demonstrated clinical feasibility against multiple targets, with advanced engineering strategies, including cytokine armoring, bispecific constructs, and locoregional delivery, beginning to address fundamental barriers such as poor tumor infiltration, limited persistence, and antigen escape. Immune checkpoint inhibitors, while largely ineffective as monotherapy in unselected populations, induce durable responsesin molecularly defined subsets such as mismatch repair-deficient and hypermutated tumors. Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.  \nKeywords Antibody–drug conjugates · CAR T cell therapy · Immune checkpoint inhibitors · Immunotherapy · Neuroblastoma · Pediatric solid tumors · Tumor microenvironment  \nIntroduction: the urgent need for novel pediatric solid tumor therapies  \nDespite decades of progress, childhood solid tumors remain a leading cause of disease-related mortality in high-income settings [1] . Relapsed or refractory disease continues to carry a poor prognosis: In high-risk neuroblastoma, eventfree survival after relapse remains persistently low; in  \nMahsa Fatahichegeni and Mohammad Amin Ansarian have contributed equally to this work and share first authorship.  \n* Mohammad Amin Ansarian [maansarian01@gmail.com](maansarian01@gmail.com)  \n* Ruiming Shi [shiruiming75@126.com](shiruiming75@126.com)  \n1 Department of Pediatrics, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China  \nosteosarcoma, 5-year overall survival (OS) after relapse remains below 30%; and recurrent medulloblastoma is associated with limited survival and substantial late toxicity [2–4] .  \nImmune checkpoint blockade has transformed outcomesin several adult cancers, epitomized by durable survival benefits with nivolumab ± ipilimumab in advanced melanoma [5] . Pediatric oncology has similarly seen success in hematologic malignancies, where anti-CD19 CAR T cell therapy (tisagenlecleucel) achieves high complete remission rates and durable disease control in children with relapsed/ refractory B cell acute lymphoblastic leukemia [6] . These advances provide the rationale to extend immunotherapy to pediatric solid tumors, though distinct tumor biology and host immunity in children necessitate tailored approaches [7] . (Fig. 1)  \nTwo key barriers restrict efficacy in pediatric solid tumors. First, most have exceptionally low tumor mutational burdens (TMB) with correspondingly sparse neoantigen  \nlandsca","cbCaisUxC8947Rcy","https://ap.wps.com/l/cbCaisUxC8947Rcy","pdf",1550189,"English","# Introduction: the urgent need for novel pediatric solid tumor therapies\n## Two key barriers restrict efficacy in pediatric solid tumors\n# The unique immune landscape of pediatric solid tumors\n## Immune-cold features in pediatric solid tumors\n# Genomic characteristics and neoantigen burden across tumor types","[{\"question\":\"Why are current immunotherapies less effective in pediatric solid tumors?\",\"answer\":\"Most pediatric solid tumors are immune-cold, featuring exceptionally low tumor mutational burden and sparse neoantigen landscapes, which reduces T cell priming. They also have profoundly immunosuppressive tumor microenvironments that blunt effector trafficking, priming, and persistence.\"},{\"question\":\"How do antibody-based therapies improve outcomes in pediatric neuroblastoma?\",\"answer\":\"Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma. Next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 broaden antibody-based strategies across pediatric tumor histologies.\"},{\"question\":\"Which emerging platforms aim to overcome barriers beyond checkpoint blockade?\",\"answer\":\"Emerging approaches include CAR T cell therapies with engineering strategies (e.g., cytokine armoring, bispecific constructs, locoregional delivery), oncolytic virotherapy, NK cell engagers, and neoantigen vaccines. These aim to address infiltration, persistence, antigen escape, and the conversion of immune-cold tumors into treatment-responsive phenotypes.\"}]","Immunotherapy for pediatric solid tumors - overcoming biological barriers through rational multimodal combinations | PDF",1790126367]