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Cancer Related Molecular Pathways / Virus-based Gene Therapy Research / Cervical Cancer and HPV Research · Journal article
The Journal of Immunology · July 28, 2026
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This is an in vitro proof-of-concept study of a rationally designed AAV transgene promoter engineered for selective activity in HPV-positive cervical cancer cells. The candidate promoter showed differential reporter expression between HPV+ cancer lines and normal epithelial controls, establishing the feasibility of targeted transgene delivery. However, no therapeutic payload has been tested, no animal or human data are provided, and clinical efficacy remains entirely unknown.
In vitro dual-luciferase reporter assay. HPV+ cervical cancer cell lines (CaSki, SiHa, C4I) and normal epithelial cells. Intervention: Synthetic AAV transgene promoter construct designed for activity in HPV-positive cells. Compared with: Normal epithelial cells (control); modulation of E2F family members to demonstrate dose-response relationship.
Candidate promoter achieved 18.31-fold increase in reporter expression in HPV16+ CaSki cells compared to normal controls 4.45-fold increase in reporter expression in HPV16+ SiHa cells compared to normal controls 15.18-fold increase in reporter expression in HPV18+ C4I cells compared to normal controls
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This preliminary work establishes a mechanistic foundation for targeted AAV-based therapy in HPV-positive cervical dysplasia. Clinicians and researchers should view this as early-stage development requiring substantial further validation in animal models and ultimately clinical trials before any therapeutic application.
In vitro proof-of-concept study demonstrating selective promoter activity in HPV-positive cervical cancer cell lines; no animal or human data, therapeutic efficacy not evaluated.
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This preliminary work establishes a mechanistic foundation for targeted AAV-based therapy in HPV-positive cervical dysplasia. Clinicians and researchers should view this as early-stage development requiring substantial further validation in animal models and ultimately clinical trials before any therapeutic application.
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Abstract Introduction Cervical cancer is the fourth most commonly diagnosed cancer in women worldwide and in some countries is the most lethal cancer in women. Ninety-nine percent of cervical cancers are attributable to HPV infection, which has decreased dramatically with the introduction of HPV vaccines. However, the incidence of cervical cancer remains high in generations of women for whom the vaccine was not available as well as in unvaccinated women, as up to 40% of eligible individuals did not receive an HPV vaccination. There is a critical unmet need for noninvasive treatment options among these groups. Methods A hallmark of HPV-mediated oncogenesis is dysregulated E2F transcription factor activity. Leveraging this, we developed a rationally designed series of synthetic AAV transgene promoters for specific activity in HPV-positive cervical cancer cells, which can then be used to deliver therapeutic payloads to tumor tissue. Our panel of candidate promoter sequences was assessed for activity in HPV+ cervical cancer cell lines as well as normal epithelial cells for expression of a luciferase reporter, as determined by comparative expression in a dual-luciferase system. Results Testing our candidate promoters in a dual luciferase reporter assay we identified a construct with activity in multiple cell lines. This candidate achieved an 18.31-fold and a 4.45-fold increase in reporter expression in HPV16+ CaSki and SiHa cancer lines compared to normal controls, respectively. Further, it produced a 15.18-fold increase in the HPV18+ C4I line compared to normal controls. By modulating the levels of activating E2F family members in normal cells, we have shown a positive relationship between E2F levels and reporter expression. Conclusion Based upon our results in vitro we have developed a candidate AAV transgene construct for specific delivery of a therapeutic payload to cervical cancer cells in vivo. Funding Source T32 Postdoctoral Fellowship Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)
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