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This mini review examines CART cell engineering strategies aimed at balancing potent cytotoxic activity with prevention of severe toxicities, particularly CRS and ICANS. It also addresses ongoing efforts to extend CAR T approaches beyond blood cancers into solid tumors, where success remains uneven.",{"@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/car-t-cell-engineering-approaches-to-minimise-toxicities/355589/",{"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-cell-engineering-approaches-to-minimise-toxicities/355589.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is toxicity management critical in CAR T cell therapy?","Question",{"text":112,"@type":113},"CAR T cells must provide strong cytotoxic activity to treat cancer, but severe toxicities can occur. Managing these risks is necessary to improve safety and broaden clinical use.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What are CRS and ICANS in CAR T cell treatment?",{"text":117,"@type":113},"CRS is associated with a sharp increase in pro-inflammatory cytokines released into the bloodstream. ICANS is a serious neurotoxicity where patients may experience encephalopathy and related neurologic symptoms.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the mini review focus on regarding engineering solutions?",{"text":121,"@type":113},"The review discusses potential solutions to overcome toxicities and improve existing CAR T cell therapies. It highlights engineering strategies intended to mitigate safety risks and enable safer administration.","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},355589,1790198405,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"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},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","TYPE Mini Review  \nPUBLISHED 15 April 2026  \nDOI 10.3389/ebm.2026.11021  \nOPEN ACCESS  \n*CORRESPONDENCE  \nCharlotte Graham,  \n [charlotte.2.graham@kcl.ac.uk](charlotte.2.graham@kcl.ac.uk)  \nRECEIVED 30 January 2026  \nREVISED 24 March 2026  \nACCEPTED 01 April 2026  \nPUBLISHED 15 April 2026  \nCITATION  \nHogben E, Schurich A and Graham C (2026) CART cell engineering approaches to minimise toxicities.  \nExp. Biol. Med. 251:11021 .  \ndoi: 10.3389/ebm.2026.11021  \nCOPYRIGHT  \n© 2026 Hogben, Schurich and Graham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nCAR T cell engineering  \napproaches to minimise toxicities  \nElizabeth Hogben 1, Anna Schurich 1 and Charlotte Graham 1,2* 1Department of Haematology, King’s College London, London, United Kingdom, 2Department of Haematology, King’s College Hospital NHS Foundation Trust, London, United Kingdom  \nAbstract  \nFor the treatment of many forms of cancer, cell-and gene-based therapies are showing promise in both pre-clinical data and clinical trials. In particular, CART cell therapies, of which there are now 7 FDA-approved products, have shown ground-breaking results in haematological cancers such as multiple myeloma and B cell malignancies. Recent research is also attempting to develop effective CAR T cell therapies for solid tumours, with varying success. One of the key challenges faced by CART cell therapy is balancing strong cytotoxic activity for an effective treatment with preventing severe and potentially lethal toxicities, such as Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome. This mini review discusses some of the potential solutions that scientists have devised to overcome toxicities and improve existing CAR T cell therapies.  \nKEYWORDS  \ncytokine release syndrome (CRS), ICANS, non-ICANS neurotoxicity, safety, toxicity, CART cell  \nImpact statement  \nWe are delighted to submit this mini review titled “CAR T cell engineering approaches to minimise toxicities,” to be considered in the special issue focused on cell and gene therapy in the journal Experimental Biology and Medicine. CAR T cell therapy has transformed the treatment landscape of haematological malignancies, and is now being investigated for use in a range of autoimmune conditions and solid cancers. However, toxicity remains a major limitation to widespread use and limits the potential target antigens available. In this mini review we have highlighted some of the engineering strategies which have been developed to try and mitigate toxicity, and which we hope will lead to safer administration. Being able to safely manage more patients in the outpatient setting would increase capacity and ultimately widen access to these life-saving therapies.  \nIntroduction  \nCell and gene therapies have made headlines in recent years through their potential demonstrated in pre-clinical data, with some breakthroughs translated into impressive clinical trial findings. A notable success story is CAR T cell therapy, which has become alifeline for patients suffering from relapsed/refractory haematological malignancies, such as multiple myeloma (MM) and B cell acute lymphoblastic leukaemia (B-ALL) . CAR T cell therapy involves isolating T cells from the patient’s blood and genetically modifying them by using a viral vector to express a chimeric antigen receptor (CAR) . This CAR enables the  \nExperimental Biology and Medicine 01  \nPublished by Frontiers Society for Experimental Biology and Medicine  \nT cell to precisely target a specific antigen expressed on cancer cells [ 1] . In the short history of CAR ","cbCailLUiaFnV7jW","https://ap.wps.com/l/cbCailLUiaFnV7jW","pdf",2080855,"English","# Introduction\n## CAR T cell therapy and CAR design\n## Toxicities and safety challenges\n## Non-ICANS neurotoxicities and related syndromes","[{\"question\":\"Why is toxicity management critical in CAR T cell therapy?\",\"answer\":\"CAR T cells must provide strong cytotoxic activity to treat cancer, but severe toxicities can occur. Managing these risks is necessary to improve safety and broaden clinical use.\"},{\"question\":\"What are CRS and ICANS in CAR T cell treatment?\",\"answer\":\"CRS is associated with a sharp increase in pro-inflammatory cytokines released into the bloodstream. ICANS is a serious neurotoxicity where patients may experience encephalopathy and related neurologic symptoms.\"},{\"question\":\"What does the mini review focus on regarding engineering solutions?\",\"answer\":\"The review discusses potential solutions to overcome toxicities and improve existing CAR T cell therapies. It highlights engineering strategies intended to mitigate safety risks and enable safer administration.\"}]","CAR T cell engineering approaches to minimise toxicities | PDF",1790120031,18]