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Virology Journal

Virology Journal

IF: 4
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Oncolytic activity of a coxsackievirus B3 strain in patient-derived cervical squamous cell carcinoma organoids and synergistic effect with paclitaxel

Published:5 October 2024 DOI: 10.1186/s12985-024-02502-y PMID: 39369233
Yanzhen Lin,?Nanyi Liu,?Chuanlai Yang,?Haoyin Tan,?Changjian Fang,?Kang Yu,?Huan Zhao,?Ningshao Xia,?Wei Wang,?Xiumin Huang,?Tong Cheng

Abstract

Background: Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035?A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids.

Methods: The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro.

Results: CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication.

Conclusions: CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Y-27632 DIHYDROCHLORIDE 146986-50-7 C14H21N3O 277 suppliers $16.00-$2691.10
Y-27632 DIHYDROCHLORIDE 146986-50-7 C14H21N3O 277 suppliers $16.00-$2691.10
Y-27632 DIHYDROCHLORIDE 146986-50-7 C14H21N3O 277 suppliers $16.00-$2691.10
Y-27632 DIHYDROCHLORIDE 146986-50-7 C14H21N3O 277 suppliers $16.00-$2691.10

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