Ann Arbor: Researchers at the University of Michigan have had initial success in mice using nanodiscs to deliver a customized therapeutic vaccine for the treatment of colon and melanoma cancer tumors. "We are basically educating the immune system with these nanodiscs so that immune cells can attack cancer cells in a personalized manner," said James Moon, the John Gideon Searle assistant professor of pharmaceutical sciences and biomedical engineering.
Personalized immunotherapy is a fast-growing field of research in the fight against cancer.
The therapeutic cancer vaccine employs nanodiscs loaded with tumor
neoantigens, which are unique mutations found in tumor cells. By
generating T-cells that recognize these specific neoantigens, the
technology targets cancer mutations and fights to eliminate cancer cells
and prevent tumor growth.
Unlike preventive vaccinations, therapeutic cancer vaccines of this type are meant to kill established cancer cells.
"The idea is that these vaccine nanodiscs will trigger the immune
system to fight the existing cancer cells in a personalized manner,"
The nanodisc technology was tested in mice with established melanoma
and colon cancer tumors. After the vaccination, twenty-seven percent of
T-cells in the blood of the mice in the study targeted the tumors.
When combined with immune checkpoint inhibitors, an existing
technology that amplifies T-cell tumor-fighting responses, the nanodisc
technology killed tumors within 10 days of treatment in the majority of
the mice. After waiting 70 days, researchers then injected the same mice
with the same tumor cells, and the tumors were rejected by the immune
system and did not grow.
"This suggests the immune system 'remembered' the cancer cells for
long-term immunity," said Rui Kuai, U-M doctoral student in
pharmaceutical sciences and lead author of the study.
"The holy grail in cancer immunotherapy is to eradicate tumors and
prevent future recurrence without systemic toxicity, and our studies
have produced very promising results in mice," Moon said.
The technology is made of extremely small, synthetic high density
lipoproteins measuring roughly 10 nanometers. By comparison, a human
hair is 80,000 to 100,000 nanometers wide.
"It's a powerful vaccine technology that efficiently delivers vaccine
components to the right cells in the right tissues. Better delivery
translates to better T-cell responses and better efficacy," said study
co-senior author Anna Schwendeman, assistant professor of pharmaceutical
The next step is to test the nanodisc technology in a larger group of larger animals, Moon said.
EVOQ Therapeutics, a new U-M spinoff biotech company, has been
founded to translate these results to the clinic. Lukasz Ochyl, a
doctoral student in pharmaceutical sciences, is also a co-author.
The study, "Designer vaccine nanodiscs for personalized cancer
immunotherapy," was published online Dec. 26 on the Nature Materials