Yale researchers have developed a groundbreaking mRNA vaccine that employs a dual-action approach to combat Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. The innovative vaccine targets the viral large T antigen protein essential for tumor cell growth while simultaneously incorporating interleukin-7 (IL-7) to enhance immune system responses, according to research published October 28 in Cell Reports.
The vaccine demonstrated potent anti-tumor effects in both animal models and patient samples, with significantly improved effectiveness when IL-7 was added to the formulation. This dual mechanism led to increased immunity and more durable anti-tumor responses against MCC, which is often caused by viral infection.
Addressing Critical Treatment Gaps
"There is an urgent need for better treatments for Merkel cell carcinoma," says the study's senior author Jeffrey J. Ishizuka, MD, DPhil, assistant professor of medicine (medical oncology and hematology) at Yale School of Medicine and a member of Yale Cancer Center. "Our vaccine aims to boost waning immunity, which may otherwise allow tumors to recur or progress."
The research addresses a significant clinical challenge: the frequent lack of durable response to MCC immune checkpoint inhibitor (ICI) therapy. The study involved 16 Yale authors from the departments of surgery, medicine (oncology), immunobiology, and pathology.
Enhanced Immune Memory for Aging Population
By incorporating IL-7 into the vaccine design, researchers aimed to strengthen T cell responses, leading to better T cell expansion, improved tumor control, and enhanced memory formation. Memory formation was a particular focus given that the aging population most at risk for MCC has an increased dependence on T cell memory compared with younger patients for achieving durable T cell responses.
The mRNA vaccine works by directing the immune response to target the viral large T antigen while co-encoding IL-7, a molecule essential for immune cell proliferation. This approach enhances T cell responses and creates a more robust and lasting anti-tumor immune response.
Promising Combination Therapy Potential
In animal models, the vaccine demonstrated excellent compatibility with anti-PD-1 immunotherapy, suggesting it could be beneficial across various treatment scenarios. These include applications before and after surgery or in combination with other systemic therapies for metastatic disease.
The synergistic effect with existing immunotherapies opens possibilities for integrated treatment approaches that could improve outcomes for patients with this challenging malignancy.
Path to Clinical Development
The research team is currently performing investigational new drug enabling studies and actively working to identify potential partners to advance the vaccine toward clinical trials. This represents a crucial step in translating the promising preclinical results into potential therapeutic benefits for patients with MCC.
The research was supported by multiple National Institutes of Health grants, including National Cancer Institute grant K08CA245112, the Yale SPORE in Skin Cancer NCI grants P50CA121974, NCI grant R37CA279822, and Yale University funding.
