Yale researchers have developed a new vaccine that does double duty against a rare and aggressive skin cancer, by targeting the protein essential to tumor cell growth and by adding a key signal to boost the immune system response, as published Oct. 28 in Cell Reports.
The mRNA vaccine directed the immune response to target viral large T antigen, a protein, and co-encoded interleukin-7 (IL-7), a molecule essential for the proliferation of immune cells, to enhance T cell responses, which led to increased immunity and a more durable anti-tumor response in Merkel cell carcinomas (MCC), often caused by a virus. The vaccine demonstrated potent effects in both animal models and patient samples and improved effectiveness when IL-7 was added.
“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 study, which addresses the frequent lack of durable response to MCC immune checkpoint inhibitor (ICI) therapy, includes 16 other Yale authors from the departments of surgery, medicine (oncology), immunobiology, and pathology.
By adding IL-7 to the vaccine, the researchers aimed to strengthen T cell response leading to better T cell expansion, improved tumor control, and memory formation. Memory was a particular focus because the aging population most at risk for MCC has an increased dependence on T cell memory, compared with younger patients, for durable T cell responses.
The study found that, in animal models, the vaccine worked well with anti-PD-1 immunotherapy, meaning it could be beneficial in other treatment scenarios including before and after surgery or in combination with other systemic therapies for metastatic disease.
The authors are currently performing investigational new drug enabling studies and working to identify potential partners to advance the vaccine toward clinical trials.