2. Academic Validation
  3. Oncolytic activity of a coxsackievirus B3 strain in patient-derived cervical squamous cell carcinoma organoids and synergistic effect with paclitaxel

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

  • Virol J. 2024 Oct 5;21(1):245. doi: 10.1186/s12985-024-02502-y.
Yanzhen Lin # 1,  Nanyi Liu # 2 3,  Chuanlai Yang 2 3,  Haoyin Tan 2 3,  Changjian Fang 2 3,  Kang Yu 2 3,  Huan Zhao 2 3,  Ningshao Xia 2 3,  Wei Wang 4 5,  Xiumin Huang 6,  Tong Cheng 7 8
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.
  • 2 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • 3 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, 361102, China.
  • 4 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, China. lukewang@xmu.edu.cn.
  • 5 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, 361102, China. lukewang@xmu.edu.cn.
  • 6 Department of Obstetrics and Gynecology, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China. huangxmxm@163.com.
  • 7 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, China. tcheng@xmu.edu.cn.
  • 8 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, 361102, China. tcheng@xmu.edu.cn.
  • # Contributed equally.
PMID: 39369233 DOI: 10.1186/s12985-024-02502-y
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.

Keywords

Cervical squamous cell carcinoma; Coxsackievirus B3; Oncolytic virus; Organoid; Virotherapy.

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