Researchers test experimental cancer vaccine in mice with aggressive melanoma

An experimental cancer vaccine that strengthens the immune system's ability to fight cancer could be combined with other cancer treatments to fight aggressive tumors, scientists from Proceedings of the National Academy of Sciences.

The researchers demonstrated that adding a molecule called Diprovocim to a vaccine could attract cancer cells to tumor sites. Their experiments on mice with melanoma suggest that these vaccines may increase the chances of healing in cases where drug therapy alone does not work.

"This co-therapy has produced a complete response – a curative response – in the treatment of melanoma," says Dale Boger, Ph.D., a research professor at Scripps, who co-directed the study.

The vaccine also encourages the immune system to fight tumor cells in case they come back, an ability that could prevent recurrence of cancer. "Just like a vaccine can cause the body to fight against external pathogens, this vaccine causes the immune system to look for the tumor," says Boger.

Developed by Boger and Beutler, Diprovocim works as an "adjuvant", a molecule added to a vaccine to trigger the body's immune response. The molecule is easy to synthesize in the laboratory and easy to modify, which makes it interesting for use in medicine.

New research shows that adding Diprovocim to a vaccine targeting cancer cells can have dramatic results.

The researchers tested the vaccine design in mice with a notoriously aggressive form of melanoma. All the mice of the experiment received anti-cancer treatment anti-PD-L1. The mice were then divided into three groups: eight received the cancer vaccine, eight received the cancer vaccine plus Diprovocim and eight received the cancer vaccine and another adjuvant called alum.

The researchers observed a survival rate of 100% over 54 days in mice given the cancer vaccine and Diprovocim. This contrasted with a zero percent survival rate in mice given only the cancer vaccine and a 25% survival rate in mice given the cancer vaccine with alum.

"It was exciting to see the vaccine work simultaneously with anti-cancer immunotherapy such as anti-PD-L1," says Boger.

Other experiments have shown that the use of Diprovocim as an adjuvant increases the cancer-fighting potential of the vaccine by stimulating the immune system to make cells known as leukocytes infiltrating tumors.

When scientists tried to restore the tumor in these mice, "that would not take," says Boger. "The animal is already vaccinated against that."

Boger says it's encouraging to see that the vaccine with Diprovocim does not have to be injected directly into a tumor. Instead, the researchers gave him an intramuscular injection away from the main site of the tumor. Vaccination required two doses administered seven days apart.

In the future, researchers plan to conduct other preclinical trials with this vaccine design and study how it works in combination with other cancer treatments.