文献类型：期刊文献

中文题名：基于KRAS突变肽段介导的胰腺癌免疫治疗

英文题名：Immunotherapy of Pancreatic Cancer Mediated by KRAS Mutant Peptides

作者：贺心怡[1];汤丁越[2];张洁[2];丁浩[1];吴侠[1]

机构：[1]华东理工大学药学院,上海200237;[2]华东理工大学生物工程学院,上海200237

年份：2025

卷号：51

期号：1

起止页码：60

中文期刊名：华东理工大学学报(自然科学版)

外文期刊名：Journal of East China University of Science and Technology

收录：;北大核心:【北大核心2023】；

语种：中文

中文关键词：胰腺导管癌;KRAS;免疫疗法;腺病毒;基因治疗

外文关键词：pancreatic ductal adenocaromas;KRAS;immunotherapy;adenovirus;gene therapy

摘要：通过增加KRAS抗原负荷来增强机体主动免疫,开发了一种KRAS靶向的免疫治疗药物。构建了Ad-SNP1、Ad-SNP2、Ad-SNP3和Ad-SNP4这4种质粒表达载体,每种载体含有的突变肽段种类、数量、排列顺序以及连接方式不同,但均包含Q61H突变肽段,同时表达载体包装腺病毒衣壳,并在体内外进行验证及筛选。结果表明,这4种表达载体都能在体外成功表达,并在小鼠体内引起免疫反应。肿瘤药效实验表明,在含有KRASQ61H突变位点的移植瘤小鼠模型中,药物可刺激体内免疫反应从而抑制肿瘤生长,但这4种药物的药效存在明显差异,Ad-SNP1载体药效最好。
Ninety percent of pancreatic ductal adenocarcinoma was induced by KRAS gene mutation in clinic.At present,there was a lack of effective targeted therapies for KRAS mutated cancer.Immunotherapy had emerged as a prominent approach for tumor treatment.This study aimed to develop a KRAS-targeted immunotherapy by enhancing immune response of anti-KRAS mutation in vivo.We constructed four plasmids with several KRAS-mutated gene sequences,HSP70 and GM-CSF.The order and linker of these KRAS-mutated gene sequences were different within these four plasmids,but they all contained the KRASQ61H mutation.These plasmids were packaged into adenovirus 5,and their capacity of anti-tumor was analyzed in vitro and in vivo.The results showed that the four plasmids could be well expressed KRAS antigen,HSP70 and GM-CSF in vitro,as well as elicited immune responses in mice.Furthermore,a pancreatic carcinoma cell line with KRASQ61H mutation,Pan02-Q61H was subcutaneously injected into mice.Among the four vectors,the Ad-SNP1 was best for inhibited the tumor growth.They also induced immune responses,led to inhibition of tumor growth in a Pan02 cells a transplanted tumor mouse models which contained KRASQ61H mutation sites,and there were significant differences in efficacy among the four drugs.We selected the Ad-SNP1 vector with the best pharmacological effect from the four drugs,laying a foundation for further research in the future,and hoping that it can provide new treatment opportunities for pancreatic cancer patients.