Cancer immunotherapy for HLA-A2, HPV+ head and neck cancer

Abstract

Problem: Recent studies indicate that the majority of oropharyngeal squamous cell carcinomas are associated with human papilloma virus (HPV) infection. Two HPV-transforming proteins, E6 and E7, are expressed in these tumors and they provide attractive targets for cancer immunotherapy. Listeria monocytogenes-based vaccines have been developed that cause regression of HPV-associated tumors in animal models. We have developed a new vaccine, Lm-ActA-E7, that is effective in treating HPV+ tumors in mice. While this vaccine works well in the context of the murine immune system, we decided to investigate whether it would work in the context of the human immune system. Methods: Mice that carry a human gene critical for presentation of foreign antigens were obtained. This gene encodes a major histocompatibility complex (MHC) molecule, HLA-A2, which is instrumental in directing lymphocytes to eliminate cancerous cells. The recombinant bacterial vaccine Lm-ActA-E7 was administered to these mice. Lymphocytes were harvested from the vaccinated mice, and then transferred to a group of mice with severe combined immunodeficiency. Human HPV+ head and neck cancers had been established in these mice prior to vaccination. Another group of mice- harboring tumors were left untreated as a control. We then observed the growth of the tumors in each group for 39 days. Results: When compared to the untreated mice, tumor growth was slowed in the mice treated with vaccinated lymphocytes. Both groups started with tumor sizes of 4 mm in diameter. The untreated tumors grew to 10 mm, while the size of the treated tumors remained stable for the duration of the experiment. Conclusion: Our recombinant bacterial vaccine slows tumor growth in the context of a human gene critical for antigen presentation. Significance: These results indicate that our recombinant bacterial vaccine strategy has the potential to treat head and neck cancers that are associated with HPV infection. Support: None reported.