[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-439636-105":59,"doc-detail-439636-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","fever-inspiration-precision-engineering-for-safe-and-systemic-immunotherapy","Fever Inspiration - Precision Engineering for Safe and Systemic Immunotherapy","","Fever Inspiration reviews engineered fever therapy (EFT) and explains why precise, safe induction of systemic immune activation matters for cancer immunomodulation. It addresses key barriers—unpredictable temperature fluctuations and inconsistent immune responses—then presents thermal immunotherapy as a solution by combining precision thermal control with nanotechnology to target fever-range temperatures (38.5–40 °C) in tumor sites. The review summarizes molecular and physiological fever foundations, evaluates therapeutic potential, and assesses recent progress, opportunities, and main clinical translation challenges.",{"@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/fever-inspiration-precision-engineering-for-safe-and-systemic-immunotherapy/439636/",{"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/fever-inspiration-precision-engineering-for-safe-and-systemic-immunotherapy/439636.png","ImageObject",300,407,{"name":92,"@type":93},"Putri","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-29",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},"What is engineered fever therapy (EFT) and what is its therapeutic goal?","Question",{"text":113,"@type":114},"EFT bioengineers systemic fever to elevate core body temperature and enhance immune-mediated disease management, particularly in oncology. It activates systemic immune responses through fever-related physiological mechanisms.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is achieving safe and controllable EFT challenging?",{"text":118,"@type":114},"Precise and safe EFT is difficult because temperature fluctuations can be unpredictable and immune responses can be inconsistent. These issues increase safety concerns such as uncontrolled hyperthermia.",{"name":120,"@type":111,"acceptedAnswer":121},"How does thermal immunotherapy improve control compared with whole-body fever?",{"text":122,"@type":114},"Thermal immunotherapy applies localized hyperthermia to pathological tissues to enhance immune activity and eliminate aberrant cells. Nanomedicine-based approaches enable tunable spatiotemporal control over thermal distribution, duration, and intensity.","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},439636,1790812967,{"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":46,"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":31,"preview_page_count":4},962085571259,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","REVIEW  \n[www.advancedscience.com](www.advancedscience.com)  \nFever Inspiration: Precision Engineering for Safe and Systemic Immunotherapy  \nYang Li, Fulong Man, Jianwei Cheng, Li Chen, Yongyong Li,* and Haiqing Dong*  \nFever, a conserved physiological response, orchestrates robust immunomodulation with significant therapeutic potential. Engineered fever therapy (EFT) leverages this mechanism to activate systemic immune response, emerging as a transformative adjuvant strategy for disease management, particularly in oncology. However, achieving precise and safe EFT remains challenging, largely due to unpredictable temperature fluctuations and inconsistent immune responses. To address these limitations, thermal immunotherapy integrates precision thermal modulation with nanotechnology, enabling targeted induction offever-range temperatures (38.5–40 °C) within tumor sites. Building upon physiological fever mechanisms and precision bioengineering, controllable EFT establishes a new paradigm with three core principles: i) precise fever induction with input and process control, ii) quantitative reprogramming of immune pathways, and iii) enhanced safety through optimized fever dynamics. This review comprehensively summarizes the molecular and physiological underpinnings offever, evaluates its therapeutic potential in disease management, and presents recent progress in thermal immunotherapy and the EFT. Furthermore, future perspectives for controllable EFT are discussed and critically assessed, along with its opportunities and main challenges for clinical translation in precision oncology.  \n1. Introduction  \nCancer represents a formidable global public health challenge, characterized by its high incidence and mortality rates. [1] According to the International Agency for Research on Cancer, ≈20 million new cancer cases and 9.7 million cancer-related deaths were reported worldwide in 2022 . [2] Despite advances in conventional surgery, chemotherapy, and radiotherapy, their clinical efficacy is still limited by systemic toxicity, residual tumors, and uncontrolled metastases. [3] Metastatic tumors, the leading cause of cancer mortality, remain particularly refractory to current interventions, underscoring a critical unmet need in oncology.[4,5] Thus, the development of precision therapies capable of addressing both primary and metastatic disease has become an urgent imperative.  \nFever is a systemic immune response to infection that plays a crucial role in immunomodulation as an evolutionarily conserved physiological mechanism. [6,7] Briefly, fever activates innate and adaptive immune responses through multiple mechanisms, including enhanced  \nY. Li, H. Dong  \nKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of Education  \nTongji Hospital Department of Pharmacy School of Medicine Tongji University Shanghai 200065, China  \nE-mail: [inano_donghq@tongji.edu.cn](inano_donghq@tongji.edu.cn)  \nF. Man, J. Cheng, L. Chen, Y. Li Shanghai Skin Disease Hospital  \nThe Institute for Biomedical Engineering and Nano Science (iNANO)  \nSchool of Medicine Tongji University Shanghai 200331, China  \nE-mail: [yongyong_li@tongji.edu.cn](yongyong_li@tongji.edu.cn)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202513566](https://doi.org/10.1002/advs.202513566)[ ](https://doi.org/10.1002/advs.202513566)© 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.1002/advs.202513566  \nmigration and activation of immune cells (e.g., macrophages and natural killer (NK) cells) and the release of pro-inflammatory cytokines. [8–12] Given the immunomodulatory effects of fever, its therapeutic significance is increasingly recognized, particularly in cancer th","cbCaigH8LSnldjjM","https://ap.wps.com/l/cbCaigH8LSnldjjM","pdf",5591091,"English","# Introduction\n## Fever as a conserved immune mechanism\n## Limits of current fever induction and rationale for EFT\n## Thermal immunotherapy for localized hyperthermia\n## Nanomedicine-enabled spatiotemporal thermal control","[{\"question\":\"What is engineered fever therapy (EFT) and what is its therapeutic goal?\",\"answer\":\"EFT bioengineers systemic fever to elevate core body temperature and enhance immune-mediated disease management, particularly in oncology. It activates systemic immune responses through fever-related physiological mechanisms.\"},{\"question\":\"Why is achieving safe and controllable EFT challenging?\",\"answer\":\"Precise and safe EFT is difficult because temperature fluctuations can be unpredictable and immune responses can be inconsistent. These issues increase safety concerns such as uncontrolled hyperthermia.\"},{\"question\":\"How does thermal immunotherapy improve control compared with whole-body fever?\",\"answer\":\"Thermal immunotherapy applies localized hyperthermia to pathological tissues to enhance immune activity and eliminate aberrant cells. Nanomedicine-based approaches enable tunable spatiotemporal control over thermal distribution, duration, and intensity.\"}]","Fever Inspiration - Precision Engineering for Safe and Systemic Immunotherapy | PDF",1790689619]