Researchers at Chiba University in Japan have developed a new nasal therapeutic vaccine as a non-invasive treatment option for cervical cancer.  

Cervical cancer is primarily caused by the human papillomavirus (HPV), but there are no approved therapeutic medicines to treat existing infections or HPV-associated cancers. 

The researchers developed a therapeutic HPV vaccine that could provide a treatment option for individuals already infected with the virus. Nasal vaccines trigger an immune response at the mucosal surface, which contributes to the protection of distant mucosal sites, including the reproductive tract, and acts as a protective barrier against pathogens and foreign particles. 

The team had previously found that nasal immunisation produced strong immune responses in the reproductive tract against herpes simplex virus type 2 (HSV-2). 

Building on this idea, the researchers used cationic nano-sized hydrogel particles called cCHP nanogels to deliver HPV antigens directly to nasal mucosal tissues. These nanogels are made of positively charged cholesteryl groups that form small spherical structures. Their positive charge allows them to adhere to negatively charged nasal mucosal surfaces, where they gradually release the antigens. 

“We have developed an intranasal therapeutic vaccine as a non-surgical alternative to conventional treatments that can compromise women’s quality of life. This novel nasal vaccine activates the mucosal homing pathways of lymphocytes, allowing it to trigger an immune response in the cervical mucosa, a site from the nasal administration,” said Associate Professor Rika Nakahashi-Ouchida. 

Immune response in animal models

The vaccine targets E7 oncoprotein, which is produced by HPV16, one of the most common high-risk strains associated with cervical cancer. This protein inactivates the key tumour suppressor pRb, which normally helps prevent cancer formation. To strengthen the immune response, the researchers added cyclic-di-AMP (c-di-AMP), an immune-boosting adjuvant that enhances T-cell-mediated immunity, encouraging the body’s T cells to attack infected or cancerous cells directly. 

In mouse models, the formulation, called cCHP-E7 + c-di-AMP, significantly slowed tumour growth compared with control groups. In macaques, after four doses, the vaccinated animals developed high levelsof E7-specific helper and killer T cells that produced immune molecules associated with tumour control. The control animals did not show this immune response.  

Importantly, immune activity was also detected in the cervical tissue, suggesting that the nasal vaccine successfully triggered protection where it is most needed. Even four months after the final dose, E7-specific killer T cells remained active, indicating a lasting immune defence against HPV-related cancer.

Diana Turner, Deputy Editor, DDW