Fusogenic vesicular stomatitis virus combined with natural killer T cell immunotherapy controls metastatic breast cancer

Sep 21, 2026

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Metastatic breast cancer is a major cause of cancer death, and existing therapies often bring adverse side effects and limited durable benefit, especially in metastatic triple negative breast cancer. The study evaluates a pre-clinical strategy that combines fusogenic oncolytic vesicular stomatitis virus engineered to express fusion-associated small transmembrane proteins p14 or p15 with natural killer T cell activation delivered via adoptive transfer of α-galactosylceramide-loaded dendritic cells. In 4T1 triple negative models, combination treatment markedly reduces metastatic lung burden and induces immune memory upon rechallenge.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusion

Keywords

Nelson et al. Breast Cancer Research (2024) 26:78 Breast Cancer Research [https://doi.org/10.1186/s13058-024-01818-5](https://doi.org/10.1186/s13058-024-01818-5) RESEARCH Open Access Fusogenic vesicular stomatitis virus combined with natural killer T cell immunotherapy controls metastatic breast cancer Adam Nelson 1,2, Nichole McMullen 1, Simon Gebremeskel 1,2, Roberto De Antueno 1, Duncan Mackenzie 1, Roy Duncan 1,2,3,4 and Brent Johnston 1,2,5* Abstract Background Metastatic breast cancer is a leading cause of cancer death in woman. Current treatment options are often associated with adverse side effects and poor outcomes, demonstrating the need for effective new treatments. Immunotherapies can provide durable outcomes in many cancers; however, limited success has been achieved in metastatic triple negative breast cancer. We tested whether combining different immunotherapies can target metastatic triple negative breast cancer in pre-clinical models. Methods Using primary and metastatic 4T1 triple negative mammary carcinoma models, we examined the therapeutic effects of oncolytic vesicular stomatitis virus (VSVΔM51) engineered to express reovirus-derived fusion associated small transmembrane proteins p14 (VSV-p14) or p15 (VSV-p15) . These viruses were delivered alone or in combination with natural killer T (NKT) cell activation therapy mediated by adoptive transfer of α-galactosylceramideloaded dendritic cells. Results Treatment of primary 4T1 tumors with VSV-p14 or VSV-p15 alone increased immunogenic tumor cell death, attenuated tumor growth, and enhanced immune cell infiltration and activation compared to control oncolytic virus (VSV-GFP) treatments and untreated mice. When combined with NKT cell activation therapy, oncolytic VSV-p14 and VSV-p15 reduced metastatic lung burden to undetectable levels in all mice and generated immune memory as evidenced by enhanced in vitro recall responses (tumor killing and cytokine production) and impaired tumor growth upon rechallenge. Conclusion Combining NKT cell immunotherapy with enhanced oncolytic virotherapy increased anti-tumor immune targeting of lung metastasis and presents a promising treatment strategy for metastatic breast cancer. Keywords Natural killer T cells, Vesicular stomatitis virus, Triple negative breast cancer, Fusion associated small transmembrane proteins, Adoptive transfers, α-galactosylceramide, Anti-tumor immunity, Oncolytic viruses, Immunotherapy *Correspondence: Brent Johnston [Brent.Johnston@dal.ca](Brent.Johnston@dal.ca) 1Department of Microbiology and Immunology, Dalhousie University, B3H 4R2 Halifax, NS, Canada 2Beatrice Hunter Cancer Research Institute, B3H 4R2 Halifax, NS, Canada 3Department of Biochemistry and Molecular Biology, Dalhousie University, B3H 4R2 Halifax, NS, Canada 4Department of Pediatrics, Dalhousie University, B3H 4R2 Halifax, NS, Canada 5Department of Pathology, Dalhousie University, B3H 4R2 Halifax, NS, Canada © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/]

FAQs

What therapy combination is tested for metastatic triple negative breast cancer?

The study combines oncolytic vesicular stomatitis virus engineered to express VSV-p14 or VSV-p15 with natural killer T cell activation therapy via adoptive transfer of α-galactosylceramide-loaded dendritic cells.

How were the experiments conducted in pre-clinical models?

Using primary and metastatic 4T1 triple negative mammary carcinoma models, researchers compared VSV-p14 or VSV-p15 alone and in combination with NKT activation, assessing tumor growth and immune responses.

What outcomes were observed in metastatic lung burden and immune memory?

Combined treatment reduced metastatic lung burden to undetectable levels in all mice and generated immune memory, shown by enhanced in vitro recall responses and impaired tumor growth upon rechallenge.

Sep 21, 2026

Upload by Eliana