Effective mRNA-based therapy using E7 antigen and IL-12 cytokine in head and neck cancer mice models

Abstract

The incidence of head and neck cancer (HNC) caused by human papillomavirus (HPV) has increased over the past several years. The mEER murine model mimicking HNC showed relatively low efficacy following E6 and E7 immunotherapy. Therefore, this study aimed to examine the anti-tumor and anti-metastatic effects of mRNA vaccines encoding HPV 16 E7, Interleukin-12 (IL-12), and Granulocyte-Macrophage colony-stimulating factor (GM-CSF) in mEER tumor-bearing mice. C57BL/6 mice were injected with cultured mEER cells and immunized with mRNA-LNPs encoding HPV16 E7, GM-CSF, and IL-12. Tumor growth was monitored, and immune responses were analyzed using flow cytometry and Enzyme-Linked ImmunoSpot assays. When immunized with both E7 and IL-12 mRNA, the tumor size dramatically decreased regardless of tumor size, while the expression of MHC1 on tumor cells increased significantly. No tumors developed upon mEER cell re-implantation. Local expression of IL-12 via mRNA delivery revealed no evidence of toxicity or reduced T-cell exhaustion markers. Furthermore, mIL-12 immunization with mE7 induces E7-specific memory T cells in lung tissues, suggesting a defense against potential metastasis and recurrence. Immunization with E7 and IL-12 mRNA is a highly effective treatment option for patients with HPV–positive HNC and is potentially applicable to other cancers.