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Review
. 2024 Mar 2;25(5):2925.
doi: 10.3390/ijms25052925.

Sindbis Virus Vaccine Platform: A Promising Oncolytic Virus-Mediated Approach for Ovarian Cancer Treatment

Christine Pampeno  1 , Silvana Opp  2 , Alicia Hurtado  1 , Daniel Meruelo  1
Affiliations
Review

Sindbis Virus Vaccine Platform: A Promising Oncolytic Virus-Mediated Approach for Ovarian Cancer Treatment

Christine Pampeno et al. Int J Mol Sci. .

Abstract

This review article provides a comprehensive overview of a novel Sindbis virus vaccine platform as potential immunotherapy for ovarian cancer patients. Ovarian cancer is the most lethal of all gynecological malignancies. The majority of high-grade serous ovarian cancer (HGSOC) patients are diagnosed with advanced disease. Current treatment options are very aggressive and limited, resulting in tumor recurrences and 50-60% patient mortality within 5 years. The unique properties of armed oncolytic Sindbis virus vectors (SV) in vivo have garnered significant interest in recent years to potently target and treat ovarian cancer. We discuss the molecular biology of Sindbis virus, its mechanisms of action against ovarian cancer cells, preclinical in vivo studies, and future perspectives. The potential of Sindbis virus-based therapies for ovarian cancer treatment holds great promise and warrants further investigation. Investigations using other oncolytic viruses in preclinical studies and clinical trials are also presented.

Keywords: Sindbis virus; immunotherapy; oncolytic virus; ovarian cancer.

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Conflict of interest statement

All authors are employed by NYU Langone School of Medicine and have no employment relationship or consultancy agreement with Cynvec, a biotechnology company that supports some studies under a Research and Licensing agreement with NYU. S.O., A.H., C.P., and D.M. are inventors on one or several issued patents and/or patent applications held by NYU that cover the Sindbis treatment of neoplasia and COVID-19. As part of the Research and Licensing agreement, the authors who are inventors on patents are entitled to a portion of the royalties that NYU Langone would receive, should Sindbis vectors be approved by the FDA for therapeutic or vaccination use. Data and materials availability: Correspondence should be addressed to D.M.

Figures

Figure 1
Figure 1
Preparation of SV vector. Plasmids are linearized, transcribed by T7 polymerase and capped in vitro. Transcripts are electroporated into BHK cells and viral vectors harvested from media [148]. T7, transcription promoter; Psg, Sindbis subgenomic promoter; GOI, gene of interest; AAA poly A tail; BHK, baby hamster kidney cells. Created with Biorender.
Figure 2
Figure 2
SV/Fluc vectors detect syngeneic MOSEC metastases in the peritoneum of immunocompetent C57BL/6 mice. Left panel: Four weeks after intraperitoneal injection (i.p.) of 1 × 107 MOSEC cells, mice were treated with a single i.p. injection of SV/Fluc vectors (~107 transducing units) and IVIS imaged the next day. Tumor free control mice were injected with SV/Fluc and imaged in parallel (Right panel) [125].
Figure 3
Figure 3
Mice treated with either SV.IL-12 or SV.IgGOX40.IL-12 at day 140 were rechallenged with MOSEC cells. The survivor mice were protected from recurrence after rechallenge [114,148].
Figure 4
Figure 4
Summary of synergistic immune stimulating anti-tumor mechanism of armed SVs via (1) direct tumor oncolysis and (2) tumor influx of activated immune cells that enhance the anti-tumor response in the tumor microenvironment (TME) [114].
See this image and copyright information in PMC

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