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Research aims to broaden CAR T therapy beyond B-ALL across hematologic malignancies, solid tumors, and brain tumors. Current advances include CAR designs and combination strategies to enhance efficacy and safety, plus future trial directions for lower-intensity regimens. However, high biopharma development costs constrain commercialization, necessitating new business models despite substantial remaining research needs.",{"@graph":69,"@context":123},[70,84,106],{"@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/car-t-cells-the-missing-piece-needed-to-improve-outcomes-for-children-with-cancer/344635/",{"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/car-t-cells-the-missing-piece-needed-to-improve-outcomes-for-children-with-cancer/344635.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why have outcomes for childhood B-ALL improved more than for many other pediatric cancers?","Question",{"text":113,"@type":114},"B-ALL has benefited from CAR-T cell activity and CD19-targeted bispecific antibodies, while progress against other pediatric cancers has largely stalled because many adult-optimized immunotherapies are not active in pediatric cancers.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which pediatric cancers and targets are described as having promising CAR-modified T cell activity?",{"text":118,"@type":114},"The text highlights activity in neuroblastoma and diffuse midline glioma (GD2), pediatric sarcomas (Her2), Hodgkin’s disease (CD30), T cell lymphoblastic leukemia (CD5 or CD7), and CAR19-refractory B-ALL (CD22), plus additional candidate targets found via surfaceome profiling such as GPC2/GPC3 and MHC-bound peptides from PHOX2B.",{"name":120,"@type":111,"acceptedAnswer":121},"What next-generation CAR T approaches are expected to improve efficacy while maintaining safety?",{"text":122,"@type":114},"The document points to therapeutics incorporating suicide domains, regulatory circuits, logic gating, and potency enhancements, along with combination immunotherapies.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},344635,1790106301,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":19,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":52},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Open access Commentary  \n CAR T cells: the missing piece needed  \nto improve outcomes for children with cancer?  \nCrystal Mackall   \nTo cite: Mackall C. CAR T  \ncells: the missing piece needed to improve outcomes forchildren with cancer? Journal for ImmunoTherapy of Cancer 2026;14:e013325 . doi:10 . 1136/ jitc-2025-013325  \nAccepted 04 December 2025  \n© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \nCenter for Cancer Cell Therapy, Stanford Cancer Institute; Parker Institute for Cancer Immunotherapy; Division of Pediatric Hematology/Oncology/ Stem Cell Transplantation and Regenerative Medicine, Dept of Pediatrics; Division of Bone Marrow Transplantation and Cell Therapy, Dept of Medicine, Stanford University School of Medicine, Stanford, California, USA  \nCorrespondence to  \nDr Crystal Mackall; [cmackall@stanford.edu](cmackall@stanford.edu)  \nABSTRACT  \nB cell acute lymphoblastic leukemia (B-ALL) is the most common cancer of childhood. Outcomes for B-ALL have steadily improved over the last five decades, most recently due to impressive activity of chimeric antigen receptor modified T (CAR-T) cells and bispecific antibodies targeting CD19 . In contrast, progress against other pediatric cancers has largely stalled. Significant academic effort is underway to expand the reach of CAR T cell therapy in pediatric cancer beyond B-ALL to other hematologic malignancies, solid cancers and brain tumors. Promising clinical activity using CAR-modified T cells has already been demonstrated in neuroblastoma and diffuse midline glioma by targeting the GD2 ganglioside, in pediatric sarcomas by targeting Her2, in Hodgkin’s disease by targeting CD30, in T cell lymphoblastic leukemia by targeting CD5 or CD7, and in CAR19 refractory B-ALL by targeting CD22 . Comprehensive surfaceome profiling of pediatric tumors is revealing additional novel candidate CAR targets expressed on pediatric cancers, including oncofetal cell surface antigens such as GPC2 and GPC3, which are expressed broadly on pediatric solid and brain tumors, and major histocompatibility complex bound peptides from oncofetal intracellular proteins such as PHOX2B. Nextgeneration CAR T cell therapeutics that incorporate suicide domains, regulatory circuits, logic gating and potency enhancements as well as combination immunotherapies are expected to further augment efficacy while maintaining safety. Current trials are administering CAR T cells inpatients with refractory disease, but future studies are warranted to determine whether adjuvant use of CAR T cells could deliver cures with lower intensity standard therapy regimens and thereby reduce long-term toxicities in pediatric cancer survivors. Despite this scientific and clinical progress, the high cost of developing CAR T cells through the traditional biopharma pathway is limiting latestage clinical development, necessitating the creation of new business models to commercialize CAR T cells for these small markets. CAR T cells hold great promise for improving outcomes for pediatric patients with cancer, but substantial additional research and clinical development is needed if this promise is to be realized for children afflicted with cancer.  \nSince the founding of the Society for the Immunotherapy of Cancer in 1984, treatment of adult cancers has undergone a metamorphosis, in large part due to immunotherapies that  \nincrease cures with less toxicity compared with cytotoxic chemotherapy and radiotherapy. Treatment of pediatric cancers over that same period tells a very different story. Cytotoxic chemotherapy remains the backbone of standard pediatric cancer regimens and radiation therapy is commonly employed.“Cures” delivered with these regimens come at the cost of lifelong late effects that increase in incidence and severity overtime and dramatically reduce the healthspan and lifespan of survivors. Immunotherapy has the potential to incre","cbCaidIpSaPk8Q0Q","https://ap.wps.com/l/cbCaidIpSaPk8Q0Q","pdf",206042,"English","# Abstract\n## Pediatric cancer challenges and limited immunotherapy activity\n## Expansion of CAR T targets across cancers\n## Next-generation CAR designs and combination approaches\n## Future trial directions and cost barriers","[{\"question\":\"Why have outcomes for childhood B-ALL improved more than for many other pediatric cancers?\",\"answer\":\"B-ALL has benefited from CAR-T cell activity and CD19-targeted bispecific antibodies, while progress against other pediatric cancers has largely stalled because many adult-optimized immunotherapies are not active in pediatric cancers.\"},{\"question\":\"Which pediatric cancers and targets are described as having promising CAR-modified T cell activity?\",\"answer\":\"The text highlights activity in neuroblastoma and diffuse midline glioma (GD2), pediatric sarcomas (Her2), Hodgkin’s disease (CD30), T cell lymphoblastic leukemia (CD5 or CD7), and CAR19-refractory B-ALL (CD22), plus additional candidate targets found via surfaceome profiling such as GPC2/GPC3 and MHC-bound peptides from PHOX2B.\"},{\"question\":\"What next-generation CAR T approaches are expected to improve efficacy while maintaining safety?\",\"answer\":\"The document points to therapeutics incorporating suicide domains, regulatory circuits, logic gating, and potency enhancements, along with combination immunotherapies.\"}]","CAR T cells: the missing piece needed - to improve outcomes for children with cancer? | PDF",1790054715]