MIT engineers create nanoparticles for delivering personalized cancer vaccines.
MIT researchers engineered a modified bacteriophage into a nanoscale vaccine carrier whose antigen density can be tuned, and it protected mice against tumors in two experiments.
Engineers at MIT have developed a nanoscale particle that could serve as a customizable delivery vehicle for personalized cancer vaccines. Its backbone is M13, a harmless bacteriophage that forms a nanofiber, which the team coats with cancer antigens. The study appears in the journal Advanced Healthcare Materials. Angela Belcher is the senior author, and Shengnan Huang of the Koch Institute is the lead author.
To build a vaccine, the researchers attach an antigen to the end of a viral coat protein called pVIII by adding the antigen's gene to the virus's DNA. Earlier work from the lab suggested that the density of antigens on the surface affects the strength of the immune response. Huang found that adding one or two negatively charged amino acids to the protein sequence raised the density, and that a genetic mutation slowing antigen production allowed further fine-tuning.
The team also changed the virus's genetic sequence to strengthen its own ability to act as an adjuvant, a component that helps stimulate immunity. According to the researchers, M13 can do this because its single-stranded DNA activates the TLR9 pathway in the innate immune system. Belcher said the design means the adjuvant no longer has to be added separately, because it is genetically encoded.
Using a model antigen called SIINFEKL, the researchers made phages with densities from 6 percent to 70 percent. They tested the 6 percent and 35 percent versions in mice, and the 35 percent version was more protective. Mice given it were much less likely to develop tumors when later exposed to melanoma cells expressing SIINFEKL, and they produced more T cells aimed at the antigen. Dendritic cells were more likely to take up the higher-density particles.
In a second experiment, the team built a vaccine carrying ADPGK, a neoantigen expressed by colon tumors in a mouse model. Mice given the higher-density version were much less likely to develop colon tumors. This study tested prevention, while the group's earlier work adapted the approach to treat colon tumors that had already formed in mice. The researchers hope to apply it to other cancers.
Belcher said the platform is “modular and we could switch out different antigens on demand.” Alberto Danielli of the University of Bologna, who was not involved, said, “I look forward to seeing whether this platform is also effective against established tumors.” Funding came partly from the Koch Institute Frontier Research Program, the Marble Center for Cancer Nanomedicine, and DARPA.
At a Glance
- The study appeared in Advanced Healthcare Materials, with Angela Belcher as senior author and Shengnan Huang as lead author.
- Researchers made phages displaying the SIINFEKL antigen at densities from 6 percent to 70 percent.
- In mice, the 35 percent density vaccine was more protective than the 6 percent version.
- A vaccine carrying the ADPGK neoantigen made mice much less likely to develop colon tumors in a mouse model.
Sources
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