MIT engineers create nanoparticles for delivering personalized cancer vaccines

MIT Engineers Unveil Nanoscale Platform to Deliver Customizable Cancer Vaccines

“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,” Angela Belcher, senior author of the study and a professor of biological engineering and materials science and engineering at MIT, explained to MIT News.

The development offers a potential pathway for creating customizable delivery vehicles tailored to personalized cancer vaccines. The research, published in the journal Advanced Healthcare Materials, demonstrates that by precisely controlling the density of cancer proteins coating the viral nanofiber, researchers can construct a vaccine capable of preventing colon tumor development in mouse models.

Building a Viral Scaffold for Medical Applications

For more than two decades, Belcher’s laboratory has deployed the M13 bacteriophage across various technological applications. Composed of a single strand of DNA encased in a protein shell known as a capsid, the virus is entirely harmless to humans. Past projects from the lab leveraged these viral scaffolds—coated with inorganic materials—to build functional devices such as batteries, semiconductors, solar cells, and catalysts.

Recently, the lab shifted its focus toward medical applications. Shengnan Huang, a research scientist at the Koch Institute and lead author of the study, noted that achieving a robust immune response requires delivering the correct antigen dosage. To control antigen density on the capsid’s long filament—formed by viral proteins called pVIII—Huang discovered that adding one or two negatively charged amino acids to the protein sequence increased density. Further fine-tuning was achieved by introducing a genetic mutation that slows down the production of the antigen protein.

While traditional vaccines typically require an added adjuvant to stimulate immune activity, the single-stranded DNA of the M13 phage naturally activates the TLR9 pathway within the body’s innate immune system.

Testing Efficacy and Preventing Tumors

To test the platform, the research team designed phages expressing an model antigen called SIINFEKL at densities ranging from 6 percent to 70 percent. Testing vaccines with 6 percent and 35 percent densities in mice revealed that the 35 percent formulation provided the highest level of protection. Mice receiving the higher-density particles generated more T cells targeting the antigen and showed a significantly lower likelihood of developing melanoma tumors when exposed to cancer cells expressing SIINFEKL.

“This interesting work adds another cog to improve the translational potential of the M13 phage platform for cancer immunotherapeutics,” said Alberto Danielli, an associate professor of molecular biology at the University of Bologna, who was not involved in the study. “I look 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.”

Future investigations aim to combat other cancer types by swapping out antigens on demand.

The research was funded by the Koch Institute Frontier Research Program, the Marble Center for Cancer Nanomedicine, and the U.S. Defense Advanced Research Projects Agency.