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Updated: Jul 20, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Effective mRNA-based therapy using E7 antigen and IL-12 cytokine in head and neck cancer mice models
Seonghyun Lee1, Jisun Lee2, Yu-Sun Lee2
1Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea.
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.
Insights
mRNA vaccines combining HPV 16 E7 and Interleukin-12 (IL-12) significantly reduced head and neck cancer (HNC) tumors in mice. This immunotherapy approach also prevented recurrence and metastasis, showing promise for HPV-positive HNC treatment.
Area of Science:
- Oncology
- Immunotherapy
- Vaccine Development
Background:
- Rising incidence of human papillomavirus (HPV)-driven head and neck cancer (HNC).
- Limited efficacy of current E6 and E7 immunotherapies in preclinical models.
- Need for novel therapeutic strategies against HPV-associated malignancies.
Purpose of the Study:
- To evaluate the anti-tumor and anti-metastatic potential of mRNA vaccines encoding HPV 16 E7, IL-12, and GM-CSF.
- To assess the safety and immune response elicited by these mRNA vaccines in a murine model.
- To explore the development of anti-tumor immunity and memory T-cell responses.
Main Methods:
- Utilized the mEER murine model for head and neck cancer.
- Administered mRNA-lipid nanoparticle (LNP) vaccines encoding HPV16 E7, IL-12, and GM-CSF.
- Monitored tumor growth, analyzed immune cell populations via flow cytometry, and assessed T-cell responses using ELISpot assays.
Main Results:
- Combined E7 and IL-12 mRNA vaccination led to significant tumor regression irrespective of initial tumor size.
- Increased MHC1 expression on tumor cells observed following IL-12 co-administration.
- No tumor development upon re-challenge, indicating durable anti-tumor immunity.
- No observed toxicity or increased T-cell exhaustion markers with local IL-12 mRNA delivery.
- Induction of E7-specific memory T cells in lung tissue, suggesting protection against metastasis.
Conclusions:
- Co-administration of HPV 16 E7 and IL-12 mRNA vaccines demonstrates potent anti-tumor and anti-metastatic effects in preclinical models.
- This combination therapy enhances anti-tumor immunity and establishes long-term memory responses.
- The developed mRNA vaccine strategy presents a promising therapeutic option for HPV-positive HNC and potentially other cancers.
