Abstract 3535: Targeting cervical cancer: VC-2 as a vaccine and treatment for HPV infections

Abstract Cervical cancer is a major cause of mortality worldwide and has been attributed to long-lasting (persistent) infections with the human papillomavirus (HPV). Although more than 50 types of HPVs are known the infect the genital tract, fewer than a dozen of them are regularly linked to cervical cancers leading to these types being designated as “high risk” HPVs. The infectious nature of HPVs procures the need for preventative vaccines against cervical cancer, and current vaccines such as Gardasil-9 and Ceravix achieve high efficacy in protection. However, once infections are established, preventative vaccines are inefficient in treating the malignancies. In HPV-associated tumors, the E7 oncoprotein is an ideal target for immunotherapeutic strategies and has been shown to be a likely target to treat cervical cancer. HSV, particularly HSV-2, often coexists with HPV due to similar transmission routes. Studies suggest that HSV infections may enhance the oncogenic effects of HPV by increasing inflammation, immune system modulation, and promoting a more favorable environment for HPV persistence and progression to cancer. Engineered Herpes Simplex Virus Type-1 (HSV-1) has been a promising candidate in treating established cancers and has been shown to be efficacious in improving anti-tumors responses and controlling tumor metastasis. Therefore, in this study, we aim to utilize the engineered HSV-1 strain (VC-2) to treat established cervical cancers and evaluate its efficacy as a prophylactic vaccine. The mice inoculated with the Tal-3 cervical cancer cell line show metastasis in the lungs and formation of large tumors. Moving forward, we would like to conduct therapeutic and prophylactic studies evaluating the reengineered VC-2 towards treating cervical cancer. Citation Format: Mohammed T. Hussain, Robert Ellis, Kiran Fida, Mariano Carossino, Brent A. Stanfield. Targeting cervical cancer: VC-2 as a vaccine and treatment for HPV infections [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3535.