Personalized Cancer Vaccine: MIT Builds It on a Virus Fiber

A personalized cancer vaccine could one day be built on a harmless virus, according to MIT engineers who have turned a modified bacteriophage into a nanofiber that carries a tunable dose of cancer antigens. In mice, the particles prevented colon tumors from developing. The study, led by Angela Belcher’s lab, appears in the journal Advanced Healthcare Materials, and MIT News reported it on 30 October.

Belcher is the James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering at MIT and a member of the Koch Institute. Shengnan Huang, a research scientist at the Koch Institute, is the lead author. Graduate students Jack Rudrum, Huaiyao Peng and Hao Nghi Luu are also authors.

How the personalized cancer vaccine is built

The backbone is M13, a bacteriophage that is harmless to humans. It consists of a single strand of DNA wrapped in a protein shell, or capsid, which forms a long filament. Belcher’s lab has used M13 for more than 20 years, engineering it to self-assemble into nanoscale 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,” Belcher said.

To make a vaccine, the team modifies one of the capsid proteins, called pVIII, by attaching an antigen to its end. This is done by adding the antigen’s gene to the virus’s DNA. The antigen is the target the immune system learns to attack.

Controlling antigen density and the built-in adjuvant

Earlier work in the lab suggested that the density of antigens on the capsid affects the strength of the immune response. Huang found she could raise the density of modified pVIII proteins by adding one or two negatively charged amino acids to the protein sequence. A genetic mutation that slows production of the antigen protein allowed further fine-tuning.

The researchers also boosted the phage’s ability to act as its own adjuvant. Most vaccines need an added adjuvant, such as aluminum hydroxide, to provoke a strong response. M13’s single-stranded DNA activates TLR9, a pathway in the body’s innate immune system, and the team strengthened this by changing the virus’s genetic sequence.

“We can control the exact length. We can control the exact antigen expression, density, pattern, the exact adjuvant amount,” Belcher said. “Now it’s all genetically encoded.”

What the mouse tests showed

The team designed phages displaying a model antigen called SIINFEKL at densities from 6% to 70%. They tested two versions in mice, at 6% and 35% density, and the 35% vaccine was the most protective.

• Mice given the higher-density particles were much less likely to develop tumors when later exposed to melanoma cells expressing SIINFEKL.
• These mice generated more T cells targeting SIINFEKL, partly because dendritic cells took up higher-density vaccines more readily.
• A second vaccine carried ADPGK, a neoantigen found only in colon tumor cells in a mouse model. Mice given the higher-density version were much less likely to develop colon tumors.

Why a modular personalized cancer vaccine matters

Because antigens can be swapped in and out, the researchers say the platform could be designed for individual patients. “For other types of cancer, we can just plug in other antigens and they can be assembled in this platform,” Huang said.

The current study tested prevention. In earlier work, the lab adapted the platform to treat colon tumors that had already formed in mice. Alberto Danielli of the University of Bologna, who was not involved, said he looks forward to seeing whether it works against established tumors and whether other antigens perform as well.

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.

As a writer, I find the reuse of a battery-making toolkit for vaccine design striking, but these are mouse results, and human testing has not been reported. For more on cancer research, see our stories on bacterial vesicles for precision cancer treatment and how cancer cells hide from immune attack.

FAQ

What is MIT’s personalized cancer vaccine made of?

It uses M13, a modified bacteriophage that is harmless to humans, which forms a nanofiber coated with cancer antigens attached to its pVIII capsid protein.

Did the vaccine work in tests?

In mice, a version with 35% antigen density protected against melanoma cells carrying a model antigen, and a neoantigen version made colon tumors much less likely.

Is it available for patients?

No. The results come from mouse studies, and the source does not report human trials or a timeline.