华东理工大学学报（自然科学版）2025，Vol.51Issue(1)：60-69,10.DOI:10.14135/j.cnki.1006-3080.20240319001
基于KRAS突变肽段介导的胰腺癌免疫治疗
Immunotherapy of Pancreatic Cancer Mediated by KRAS Mutant Peptides
贺心怡 1汤丁越 2张洁 2丁浩 1吴侠1
作者信息
- 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
- 折叠
摘要
Abstract
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.关键词
胰腺导管癌/KRAS/免疫疗法/腺病毒/基因治疗Key words
pancreatic ductal adenocaromas/KRAS/immunotherapy/adenovirus/gene therapy分类
医药卫生引用本文复制引用
贺心怡,汤丁越,张洁,丁浩,吴侠..基于KRAS突变肽段介导的胰腺癌免疫治疗[J].华东理工大学学报（自然科学版）,2025,51(1):60-69,10.
