Experimental Vaccine-Adjuvant Combination Eliminates Melanoma in Mice

A team of scientists from the Scripps Research Institute and the University of Texas Southwestern Medical Center has demonstrated that adding an ‘adjuvant’ molecule called diprovocim to a new vaccine can draw cancer-fighting cells to tumor sites.

An experimental vaccine that boosts the immune system’s ability to fight cancers could work in tandem with other cancer therapies to fight aggressive tumors. Image credit: Julio C. Valencia, NCI Center for Cancer Research.

An experimental vaccine that boosts the immune system’s ability to fight cancers could work in tandem with other cancer therapies to fight aggressive tumors. Image credit: Julio C. Valencia, NCI Center for Cancer Research.

“This co-therapy produced a complete response — a curative response — in the treatment of melanoma,” said study co-author Professor Dale Boger, from the Department of Chemistry at the Scripps Research Institute.

The new vaccine prompts the immune system to fight tumor cells should they ever return, a capability that could prevent cancer recurrence.

“Just as a vaccine can train the body to fight off external pathogens, this vaccine trains the immune system to go after the tumor,” Professor Boger noted.

Developed by Professor Boger and Nobel laureate Professor Bruce Beutler, of the University of Texas Southwestern Medical Center, a compound called diprovocim works as an adjuvant.

The team tested the vaccine design on mice with a form of aggressive melanoma. All mice in the experiment were given the anti-cancer therapy anti-PD-L1.

The mice were then split into three group: eight received the cancer vaccine, eight received the cancer vaccine plus diprovocim, and eight received the cancer vaccine plus an alternative adjuvant called alum.

The researchers observed a 100% survival rate over 54 days in the mice given the cancer vaccine and diprovocim.

This was in contrast to 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.

Further experiments showed that using diprovocim as an adjuvant boosts the vaccine’s cancer-fighting potential by stimulating the immune system to make cells called tumor-infiltrating leukocytes.

“When we tried to re-establish the tumor in these mice, it wouldn’t take. The animal is already vaccinated against it,” Professor Boger said.

“It is encouraging to see that the vaccine with diprovocim does not need to be injected directly into a tumor. Instead, we gave it as an intramuscular injection away from the main tumor site. The vaccination did require two doses given seven days apart.”

Going forward, the researchers plan to do further pre-clinical testing with this vaccine design and study how it works in combination with other cancer therapies.

The findings appear in the Proceedings of the National Academy of Sciences.

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Ying Wang et al. Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice. PNAS, published online August 27, 2018; doi: 10.1073/pnas.1809232115

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