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A nanoparticle vaccine designed to fight cancers induced by human papillomavirus (HPV) eradicated tumors in an animal model of late-stage metastatic disease, UT Southwestern Medical Center scientists report in a new study published in the Proceedings of the National Academy of Sciences (PNAS). The findings could ultimately lead to a new type of vaccine that would be used to treat a variety of cancers.

“Our study provides a safe and effective way to treat cancers that have spread or cannot be surgically removed,” said Jinming Gao, Ph.D., Professor in the Harold C. Simmons Comprehensive Cancer Center and of Biomedical Engineering, Cell Biology, Otolaryngology – Head & Neck Surgery, and Pharmacology at UT Southwestern. “Creating a nanovaccine for systemic use for metastatic cancers is not easy due to potential toxicity, but we have overcome those challenges with this new therapy.”

Dr. Gao co-led the study with Shuang Chen, Ph.D., and Shuyue Ye, Ph.D., both postdoctoral researchers in the Gao Lab.

Researchers have been developing vaccines that activate the immune system to prevent various illnesses since the late 1700s. More recently, they have developed a growing number of therapeutic vaccines, which harness the immune system to manage or treat preexisting diseases, such as cancer. A nanovaccine uses tiny particles to encapsulate and deliver antigens to immune cells, triggering the body’s protective response.

HPV causes about 37,800 new cancer cases in the U.S. each year, a number that continues to grow. Although there is an effective vaccine to prevent HPV, a sexually transmitted infection, no therapeutic vaccines exist to treat HPV-related cancers. Such a vaccine would be used to treat patients with HPV-related cancers, such as cervical and head and neck cancers, that have spread or are in locations that are inaccessible to surgical interventions or where radiation therapy is not feasible, Dr. Gao explained. Few effective treatments currently exist for these disease subsets.

To develop a therapeutic vaccine against HPV-related cancers, Dr. Gao and his colleagues combined a polymer and a small-molecule drug that both activate stimulator of interferon genes (STING) – a protein that triggers immune activity – with a protein antigen called E7 derived from HPV. Together, these components formed nanoparticles about 25-30 nanometers in diameter (for comparison, 1 million nanometers equal 1 millimeter).

When the researchers examined mice that received the nanovaccine, they found it was taken up by the spleen, an organ that harbors immune cells for surveillance of foreign particles such as viruses. Nanoparticles that entered immune cells unraveled into their components, with the polymer and drug stimulating STING activity and the viral protein priming the immune system to fight against cells that carried it.

Tests showed that the nanovaccine eradicated both primary HPV-related tumors and metastatic cancer nodules that spread to other organs. In a mouse model of metastatic HPV-related lung cancer, 71% of animals that received the nanovaccine were still alive 60 days after treatment, while those that received immune checkpoint inhibitors – drugs that are considered the current gold standard for treating metastatic HPV-related cancers – died of their disease during this time. When the scientists combined the nanovaccine with the checkpoint therapy, 100% of the mice survived. The nanovaccine appeared safe, causing no organ damage, weight loss, or immune activity beyond that aimed at the cancers.

Dr. Gao said these results showcase the promise of this approach for treating HPV-related cancers and could be adapted to other cancer types by customizing the cancer-related protein targeted by the vaccine. He and his colleagues are continuing to test this approach in animal models with a plan to eventually conduct clinical trials in patients.

Read the original article on UT Southwestern Medical Center.