A Structure-Guided Genetic Modification Strategy: Developing Seneca Valley Virus Therapy against Nonsensitive Nonsmall Cell Lung Carcinoma.

ABSTRACT: Numerous studies have illustrated that the Seneca Valley virus (SVV) shows sufficient oncolytic efficacy targeting small cell lung cancer (SCLC). However, the therapeutics of nonsmall cell lung carcinoma (NSCLC, accounts for 85% of lung cancer cases) using oncolytic virus have been resisting due to the filtration of neutralizing antibody and limited reproduction capacity. Here, we employed structural biology and reverse genetics to optimize novel oncolytic SVV mutants (viral receptor-associated mutant SVV-S177A and viral antigenic peptide-related variant SVV-S177A/P60S) with increased infectivity and lower immunogenicity. The results of the NSCLC-bearing athymic mouse model demonstrated that wild-type (wt) SVV-HB extended the median overall survival (mOS) from 11 days in the PBS group to 1

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC10231241 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature