ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
GRP78 Nanobody-Directed Immunotoxin Activates Innate Immunity Through STING Pathway to Synergize Tumor Immunotherapy.
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Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Bacteriophages in the treatment of cutaneous infections and skin disorders: therapeutic advances and future directions.Clinical microbiology reviews · 2026Review
- A Radioresistant-Tumor-Targeted Nanoparticle for X-Ray-Controlled Nitric Oxide Release to Potentiate Radiotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GRP78 in viral pneumonia: dual regulatory mechanisms and translational prospects.Clinical and experimental medicine · 2026Review
- Igniting cold tumors: reprogramming the tumor immune microenvironment with dual-payload ADCs in combination with PD-L1&4-1BB bispecific antibodies.Journal for immunotherapy of cancer · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Astragalus Polysaccharides Induce Immunogenic Cell Death in Melanoma: A Mechanism Mediated by cGAS/STING Activation via Intratumoral Microbiota Modulation.Cancer medicine · 2026Article
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- GRP78 Nanobody-Directed Immunotoxin Activates Innate Immunity Through STING Pathway to Synergize Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multifaceted Applications of Nanomaterials in Colorectal Cancer Management: Screening, Diagnostics, and Therapeutics.International journal of nanomedicine · 2025Review
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Authors and funding
17 authors.
Huifang WangDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Runhua ZhouClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Chengchao XuDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Lingyun DaiDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Rui HouDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Liuhai ZhengDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Chunjin FuDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Guangwei ShiDepartment of Neurosurgery & Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Guangzhou, 510515, China.
Jingwei WangDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Yang LiDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Jinpeng CenDepartment of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Xiaolong XuDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.
Le YuClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Yilei LiClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Jigang WangSchool of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Qingfeng DuSchool of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Zhijie LiDepartment of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.ORCID https://orcid.org/0000-0002-5445-7976
Funding
CACMS Innovation Fund CI2021A05101CACMS Innovation Fund CI2021A05104CACMS Innovation Fund CI2023E002Guangdong Basic and Applied Basic Research Foundation 2021A1515012164Guangdong Basic and Applied Basic Research Foundation 2021A1515111188Guangdong Basic and Applied Basic Research Foundation 2022A1515110745HUILAN Public Welfare, Shenzhen Science and Technology Innovation Commission JCYJ20200109120205924International Science and Technology Cooperation for Shenzhen Technology Innovation Plan GJHZ20200731095411034Key Special Project of Strategic Science and Technology Innovation Cooperation from National Key R&D Program 2023YFE0204500National Key Research and Development Program of China 2022YFC2303600National Natural Science Foundation of China 32101219National Natural Science Foundation of China 82103140National Natural Science Foundation of China 82373775National Natural Science Foundation of China 82404492Natural Science Foundation of Top Talent of SZTU GDRC202125Science and Technology Foundation of Shenzhen JCYJ20200109120205924Science and Technology Foundation of Shenzhen JCYJ20210324113608023Science and Technology Foundation of Shenzhen JCYJ20210324115800001Science and Technology Foundation of Shenzhen (Shenzhen Clinical Medical Research Center for Geriatric Diseases), Shenzhen Medical Research Fund B2302051Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences CI2021B014Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences CI2023D003Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences CI2023D008Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties NO.SZGSP001Shenzhen Governmental Sustainable Development Fund KCXFZ20201221173612034Shenzhen key Laboratory of Kidney Diseases ZDSYS201504301616234Shenzhen Key Medical Discipline Construction Fund SZXK046Shenzhen Science and Technology Innovation Committee RCBS20210706092213007Shenzhen Science and Technology Innovation Committee RCYX20221008092950121
Abstract
The lack of targetable antigens poses a significant challenge in developing effective cancer-targeted therapies. Cell surface translocation of endoplasmic reticulum (ER) chaperones, such as glucose-regulated protein 78 (GRP78), during malignancy, drug resistance, and ER stress induced by therapies, offers a promising pan-cancer target. To target GRP78, nanobody C5, identified from a phage library and exhibiting high affinity for human and mouse GRP78, is utilized to develop the Pseudomonas exotoxin (PE) immunotoxin C5-PE38. C5-PE38 induced ER stress, apoptosis and immunogenic cell death in targeted cells and showed antitumor efficacy against colorectal cancer and melanoma models without obvious toxicity. Mechanistically, transcriptome profiling showed that C5-PE38 reshaped the tumor immune microenvironment with enhanced innate and adaptive immune response and response to interferon beta. Moreover, C5-PE38-induced cell death could trans-activate STING pathway in dendritic cells and macrophages, promoting CD8
Indexed as
Endoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsImmunity, InnateImmunotherapyImmunotoxinsMembrane ProteinsSingle-Domain AntibodiesAnimalsCell Line, TumorColorectal NeoplasmsExotoxinsHumansMelanomaMiceMice, Inbred C57BLTumor MicroenvironmentEndoplasmic Reticulum Chaperone BiPExotoxinsHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mouseImmunotoxinsMembrane ProteinsSingle-Domain Antibodiescell surface glucose‐regulated protein 78 (GRP78)immunotherapyimmunotoxinSTING pathwaytargeted therapy
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.