# Boosting immune response against cervical cancer: A combined approach using oncolytic virus and targeted therapies

**Authors:** Hedieh Zargaran, Amir Ghaemi, Mohammad Shenagari, Mehdi Samadi, Michael Burger, Michael Burger, Michael Burger

PMC · DOI: 10.1371/journal.pone.0312979 · PLOS One · 2025-05-22

## TL;DR

This study explores combining an oncolytic virus with two drugs to boost immune responses and reduce tumor growth in cervical cancer.

## Contribution

A novel triple therapy combining NDV, Everolimus, and Beclin-1 is proposed for HPV-related cervical cancer.

## Key findings

- Triple therapy reduced tumor growth by up to 70% compared to monotherapies.
- The treatment increased immune responses, including cytokine levels and CD8+ T cell infiltration.
- Mice receiving triple therapy showed improved survival rates.

## Abstract

Cervical cancer remains a primary reason for cancer malignancy among women worldwide, primarily due to human papillomavirus (HPV) strains HPV16 and HPV18. Despite having access to vaccines, there are few treatment options for advanced or recurring cases. This research investigates the possibility of using Newcastle disease virus (NDV) along with Everolimus (EVE) and Beclin-1 (BEC) to improve immune reactions and decrease tumor development in an experimental model of HPV-related cervical cancer.

A mouse model for cervical cancer was created by utilizing HPV16 E6/E7-expressing TC-1 cells in C57BL/6 mice. The mice underwent treatment with NDV, EVE, BEC, or various combinations of these therapies. Tumor progression was monitored, evaluated immune responses by measuring cytokine levels (including IL-4, IFN-γ, and IL-12), and investigated the presence of CD8 + T cells within the tumors. Additionally, survival rates were monitored throughout the study.

The synergy of NDV, EVE, and BEC led to a remarkable decrease in tumor growth, achieving reductions of as much as 70% when compared to monotherapies. Additionally, our combination therapy elicited strong immune reactions, evidenced by increased concentrations of IL-4, IFN-γ, and IL-12, along with enhanced infiltration of CD8 + T cells into the tumors. Mice that were subjected to this Triple therapy exhibited better survival rates than those in other treatment categories.

Our findings highlight the potential to improve outcomes in cervical cancer associated with HPV through a multi-faceted approach incorporating NDV, Everolimus, and Beclin-1. This therapeutic strategy not only hinders tumor growth but also strengthens the immune system’s ability to fight against cancer. These results prompt further exploration of this combination in clinical trials, with the goal of offering new treatment avenues for patients who have limited choices.

## Linked entities

- **Genes:** e6 (E6 protein) [NCBI Gene 929651], E7 (E7) [NCBI Gene 944319]
- **Proteins:** CD8A (CD8 subunit alpha), IL4 (interleukin 4), IFNG (interferon gamma), IL12 (Interleukin 12 level)
- **Chemicals:** Everolimus (PubChem CID 6442177)
- **Diseases:** cervical cancer (MONDO:0002974)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}
- **Diseases:** Cervical cancer (MESH:D002583), Tumor (MESH:D009369)
- **Chemicals:** EVE (MESH:D000068338)
- **Species:** Human papillomavirus (species) [taxon 10566], NDV [taxon 11176], Human papillomavirus 16 (serotype) [taxon 333760], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), TC-1 — Mus musculus (Mouse), Hybridoma (CVCL_G561)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12097584/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12097584/full.md

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Source: https://tomesphere.com/paper/PMC12097584