A new study from researchers at Chiba University presents a promising approach to treating cervical cancer using an intranasal nanogel vaccine. Currently, while the human papillomavirus (HPV) vaccine is effective in preventing infection, it does not eliminate existing infections or stop their progression to cervical cancer. The research, led by Rika Nakahashi-Ouchida, MD, and Hiromi Mori from Chiba University Hospital, was published in Science Translational Medicine on October 11, 2023.
Cervical cancer, primarily caused by persistent infections with high-risk strains of HPV, remains a significant global health issue. According to the World Health Organization, there were approximately 670,000 new cases and 350,000 deaths attributed to cervical cancer worldwide in 2022. Current treatment options, including surgery and chemotherapy, often compromise patient quality of life and fertility, highlighting an urgent need for innovative therapies.
The newly developed nasal vaccine utilizes cationic cholesteryl-group-bearing nanogels (cCHP) to target HPV antigens directly in the nasal mucosa. This delivery method allows for localized immune responses that can inhibit tumor growth. Specifically, the vaccine targets the E7 oncoprotein produced by HPV16, a prevalent high-risk strain associated with cervical cancer.
The researchers combined the E7 antigen with cyclic-di-AMP (c-di-AMP), an adjuvant known to enhance T-cell responses. The formulation, referred to as cCHP-E7 + c-di-AMP, has shown significant potential in preclinical trials. In experiments conducted on mice, the vaccine notably slowed tumor growth and induced E7-specific CD4+ and CD8+ T cells in cervicovaginal tissue. Furthermore, in macaque models, four doses administered via a nasal spray device elicited robust immune responses, sustaining levels of E7-specific killer T cells for four months post-treatment.
“We have developed an intranasal therapeutic vaccine as a nonsurgical alternative to conventional treatments that can compromise women’s quality of life,” said Nakahashi-Ouchida. This innovative approach activates the mucosal homing pathways of lymphocytes, facilitating an immune response in the cervical mucosa, which could lead to safer treatment options for patients.
The implications of this research are profound, especially in the context of cervical cancer’s disproportionate impact on low- and middle-income countries. These regions often lack adequate access to HPV vaccination and treatment options, making the quest for effective therapeutic strategies even more critical.
The findings from Chiba University indicate that nasal delivery can stimulate mucosal immunity in the reproductive tract, a concept previously demonstrated in models of herpes simplex virus. This suggests a potential shift in how cervical cancer could be treated going forward.
As the search for therapeutic options against HPV-driven cancers continues, this work underscores the transformative potential of nanogel-based nasal vaccines. By merging local immune activation with a non-invasive delivery method, this approach may help preserve fertility and enhance the overall quality of life for patients.
“Immunotherapies such as intranasal therapeutic vaccines may help establish a new category of noninvasive treatment. These approaches could be extended to recurrence prevention and chronic disease management, offering patients safer and more accessible options,” Nakahashi-Ouchida added.
While further clinical testing is essential, the research marks a significant advancement in expanding the role of immunotherapy beyond prevention, paving the way for a new generation of mucosal-targeted vaccines that could reshape cervical cancer treatment.
