Construction and Evaluation of Antitumor Efficacy of a Novel Chimeric Oncolytic Adenovirus Vector
10.3870/j.issn.1672-0741.25.02.011
- VernacularTitle:一种新型嵌合型溶瘤腺病毒载体的构建及抗肿瘤效应评估
- Author:
Jiaqi YE
1
;
Wenhuan LI
;
Zhoutong DAI
Author Information
1. 华中科技大学同济医学院附属同济医院妇产科,武汉 430030
- Publication Type:Journal Article
- Keywords:
chimeric oncolytic adenovirus;
adenovirus serotype 5;
pre-existing neutralizing antibody;
gene therapy
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(4):535-540
- CountryChina
- Language:Chinese
-
Abstract:
Objective The high global prevalence of adenovirus serotype 5(Ad5)infection,particularly in developing coun-tries,has led to widespread pre-existing neutralizing antibodies(NAbs)against this serotype.These NAbs may substantially im-pair the efficacy of Ad5-based therapeutics,necessitating the development of novel strategies to circumvent neutralizing antibody interference.Methods A novel Ad5-based vector was engineered via homologous recombination,wherein the hexon hypervari-able region(HVR)1,2,and 5 of Ad5 were strategically replaced with their counterparts from the less prevalent adenovirus sero-type 35(Ad35).This chimeric design aimed to reduce vector neutralization by Ad5-specific NAbs while preserving infectivi-ty.Results The hexon HVR-modified Ad5 vector exhibited reduced neutralization by pre-existing Ad5 antibodies while retai-ning efficient infectivity in tumor cells.In animal models,thesemodified vectors demonstrated excellent oncolyticability and still maintained strong tumor-killing activity in nude mice that received passive immunization with Ad5 neutralizing antibody ser-um.Conclusion The hexon HVR-modified Ad5 vectors demonstrate effective tumor infection rates and oncolytic efficacy in the presence of pre-existing Ad5 NAbs,suggesting promising clinical potential.
