MIT engineers have turned a harmless virus into a customizable carrier for cancer vaccines, according to a study published Oct. 30 in the journal Advanced Healthcare Materials.
The backbone of the vaccine is M13, a bacteriophage that infects bacteria but is harmless to humans. It forms a long nanofiber that can be coated with cancer antigens, the proteins the immune system learns to target. By precisely controlling the density of those antigens, the researchers created a vaccine that prevented colon tumors from developing in mice, MIT News reported.
“The great thing about this is that it’s modular and we could switch out different antigens on demand, so you could design it to be patient-specific and target a known antigen for a particular kind of cancer,” said senior author Angela Belcher, the James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research.
From batteries to vaccines
Belcher’s lab has worked with M13 for more than 20 years, engineering the virus to self-assemble into scaffolds for batteries, semiconductors, solar cells and catalysts. “Some of the lessons learned from making batteries and all these other things are now being fine-tuned to make personalized vaccines,” she said.
To build a vaccine, the team attaches an antigen to one of the virus’s coat proteins, called pVIII, by adding the antigen’s gene to the virus’s DNA. Lead author Shengnan Huang, a Koch Institute research scientist, found she could raise the antigen density by adding one or two negatively charged amino acids and fine-tune it further with a mutation that slows antigen production.
The virus can also act as its own adjuvant, the ingredient that strengthens an immune response, because its single-stranded DNA activates an innate immune pathway called TLR9. “A lot of times with a vaccine, you’ll have to put a different adjuvant with it, but now it’s all genetically encoded,” Belcher said.
What the mouse tests showed
The researchers built particles carrying a model antigen at densities from 6% to 70%. In mice, a 35% density vaccine protected better than a 6% version. Vaccinated mice were much less likely to develop tumors when later exposed to melanoma cells carrying the antigen, and they made more T cells that targeted it.
In another experiment, a higher-density vaccine carrying ADPGK, a neoantigen found in colon tumors in a mouse model, made the mice much less likely to develop colon tumors. The team’s earlier work adapted the platform to treat colon tumors that had already formed in mice.
What comes next
The work so far is in mice. Alberto Danielli, an associate professor of molecular biology at the University of Bologna who was not involved, said he looks forward to “seeing whether this platform is also effective against established tumors and whether additional tumor antigens can be displayed with comparable molecular and immunological efficacy.”
The research was funded in part by the Koch Institute Frontier Research Program, the Marble Center for Cancer Nanomedicine and the U.S. Defense Advanced Research Projects Agency.