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논문 기본 정보

자료유형
학술저널
저자정보
Jingbo Ma (Department of Hyperbaric Medicine Shenzhen People’s Hospital) Xiaolong Xu (Department of Geriatrics Shenzhen People’s Hospital) Chunjin Fu (Department of Geriatrics Shenzhen People’s Hospital) Peng Xia (Department of Hyperbaric Medicine Shenzhen People’s Hospital) Ming Tian (Department of Hyperbaric Medicine Shenzhen People’s Hospital) Liuhai Zheng (Department of Hyperbaric Medicine Shenzhen People’s Hospital) Kun Chen (Department of Hyperbaric Medicine Shenzhen People’s Hospital) Xiaolian Liu (Clinical Pharmacy Center Nanfang Hospital Southern Medical University) Yilei Li (Clinical Pharmacy Center Nanfang Hospital Southern Medical University) Le Yu (Clinical Pharmacy Center Nanfang Hospital Southern Medical University) Qinchang Zhu (College of Pharmacy Shenzhen Technology University) Yangyang Yu (Health Science Center Shenzhen University) Rongrong Fan (Deapartment of Biosciences and Nutrition Karolinska Institute) Haibo Jiang (Department of Chemistry The University of Hong Kong) Zhifen Li (School of Chemistry and Chemical Engineering Shanxi Datong University) Chuanbin Yang (Department of Geriatrics Shenzhen People’s Hospital) Chengchao Xu (Department of Geriatrics Shenzhen People’s Hospital) Ying Long (Department of Hyperbaric Medicine Shenzhen People’s Hospital) Jigang Wang (Department of Geriatrics Shenzhen People’s Hospital) Zhijie Li (Department of Hyperbaric Medicine Shenzhen People’s Hospital)
저널정보
한국생체재료학회 생체재료학회지 생체재료학회지 제26권 제4호
발행연도
2022.12
수록면
1,115 - 1,134 (20page)
DOI
https://doi.org/10.1186/s40824-022-00312-3

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Background: It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nano body targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. Methods: Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. Results: Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immu notoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. Conclusions: The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobody based immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.
#Nanobody #Cadherin-17 #Immunotoxin #Gastric cancer #Targeted therapy #Jingbo Ma #Xiaolong Xu and Chunjin Fu are contribute equally to this work and share the first-authorship.

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