Research Spotlight: New Therapeutic HPV Vaccine Shows Promise for Treating Cancer in Preclinical Studies

Yohannes Gemechu, PhD, of the Vaccine and Immunotherapy Center (VIC) within the Department of Medicine at Mass General Brigham, is the lead author of a paper published in Molecular Cancer Therapeutics, "New Therapeutic Cancer Vaccine with Lenalidomide Induces Potent T Cell Immunity and Inhibits HPV E6/E7-Expressing Tumor Growth in Mice." Mark C. Poznansky, MD, PhD, and Patrick M. Reeves, PhD, also of the VIC, are co-senior authors.

Q: What challenges or unmet needs make this study important?

Preventive vaccines for human papillomavirus (HPV) have dramatically reduced new infections, but they cannot treat cancers that have already developed. According to the World Health Organization, HPV causes approximately 630,000 new cancer cases worldwide each year, including about 39,300 cases annually in the United States. Many patients with HPV-related cancers, such as cervical and head and neck cancers, do not respond well to current treatments. Although immunotherapy has transformed cancer care, it benefits only a fraction of patients because many tumors are able to evade or suppress the body's immune system. Developing treatments that can better train the immune system to recognize and destroy cancer cells remains a major unmet medical need.

Q: What central question(s) were you investigating?

We wanted to know whether our new therapeutic cancer vaccine, VTX-067, could safely train the immune system to recognize and kill HPV-related cancer cells. We also wanted to understand how the vaccine works, whether it could provide long-lasting protection against cancer returning, and whether combining it with another immune-boosting treatment could make it even more effective.

Q: What methods or approach did you use?

We designed VTX-067 to train the immune system to recognize and attack HPV-related cancer cells. The vaccine uses a unique "plug-and-play" design in which two separate components naturally snap together. One component helps activate the immune system, while the other carries pieces of HPV proteins found only in cancer cells. This modular approach makes it possible to quickly adapt the platform to target additional cancer-related proteins or even personalized tumor antigens in the future.

We tested VTX-067 in several mouse models of HPV-related cancer, including models that closely resemble cervical cancer. We monitored tumor growth, survival and immune responses to evaluate how well the vaccine worked. We also performed experiments to identify which immune cells were responsible for eliminating tumors and investigated whether combining VTX-067 with lenalidomide, an FDA-approved immune-modulating drug, could further improve its anti-cancer activity.

Q: What did you find?

In preclinical studies, VTX-067 generated a strong immune response, slowed tumor growth, extended survival and produced long-lasting protection against cancer recurrence. The vaccine activated the body's natural cancer-fighting immune cells, enabling them to better recognize and eliminate tumors.

When combined with lenalidomide, the treatment became even more effective, producing greater tumor control than the vaccine alone, even at a suboptimal vaccine dose. Importantly, the vaccine was well tolerated, with no significant safety concerns observed in the animal studies.

Q: What are the real-world implications, particularly for patients?

These findings represent an important step toward developing a new generation of therapeutic cancer vaccines. If future clinical trials confirm our results, this strategy could offer a new treatment option for patients with HPV-related cancers and may also provide a flexible platform for developing similar vaccines against other types of cancer.

In addition, Voltron Therapeutics, Inc., a startup biotech company and licensee of the Mass General Brigham intellectual property surrounding this invention, has been a close collaborator on this work and is committed to advancing it to first-in-human testing in a clinical trial for patients with cervical cancer.

Overall, this study exemplifies how academic scientists can work successfully with industry partners-in this case, a team of experienced medical product developers and regulatory experts-to move inventions made at Mass General Brigham from bench to bedside.

Q: What are the next steps?

The next phase of development is focused on advancing VTX-067 toward clinical evaluation. A pre-Investigational New Drug (pre-IND) provided to the U.S. Food and Drug Administration (FDA) resulted in supporting the continued development of the vaccine. Comprehensive Good Laboratory Practice toxicology and safety studies are currently underway to establish the safety profile required for regulatory submission and are being funded and managed by Voltron Therapeutics, Inc.

In parallel, Good Manufacturing Practice (GMP)-grade production of VTX-067 is planned to support future clinical studies. Together, these activities are laying the foundation for first-in-human clinical trials evaluating VTX-067 in patients with HPV-positive cervical cancer and HPV-positive head and neck cancers. Additional studies will continue to optimize combination strategies and identify biomarkers that predict therapeutic response and durable clinical benefit.