Researchers at the Massachusetts Institute of Technology (MIT) have converted a harmless virus into a nanoscale delivery platform that could help develop personalized cancer vaccines. By controlling how densely cancer-targeting proteins are presented on the virus, the team developed vaccine particles that significantly reduced tumor development in mice.
The platform uses a modified bacteriophage called M13, a virus that infects bacteria but is harmless to humans. It forms a long, thread-like structure called a nanofiber that can be coated with antigens, proteins that help the immune system recognize specific targets.
The researchers found that adjusting the concentration of these antigens on the virus structure changed the effectiveness of the vaccine in stimulating an immune response. This could allow scientists to tailor the particles with different antigens to target individual patients’ tumors.
The study was led by researchers at MIT’s Koch Institute for Integrative Cancer Research. Angela Belcher, professor of biological engineering and materials science and engineering, was the lead author, while research scientist Shengnan Huang led the work.
Tuning the viral vaccine structure
The M13 bacteriophage consists of a single strand of DNA surrounded by a protein coat, a capsid. The researchers modified a capsid protein called pVIII and attached cancer antigens to its surface by incorporating the appropriate genetic instructions into the virus.
However, it was important to control how many antigen-carrying proteins appeared on the virus structure. The researchers found that adding one or two negatively charged amino acids to the pVIII protein increased antigen density. They could customize it further by introducing a genetic mutation that slows down antigen production.
Using these techniques, the team produced particles containing the model antigen SIINFEKL at densities ranging from 6 to 70 percent. In tests on mice, a vaccine with an antigen density of 35 percent provided greater protection than one with 6 percent.
Mice that received the higher density vaccine were less likely to develop tumors after being exposed to melanoma cells carrying the same antigen. They also produced more T cells that targeted the cancer-associated protein. The researchers found that dendritic cells, which help activate T cells, are more likely to take up particles with higher antigen density.
Testing protection against colon tumors
The team also tested the platform with ADPGK, a neoantigen specifically found in colon tumors in a mouse model. Neoantigens are proteins that arise from changes in cancer cells and can help the immune system distinguish tumors from healthy tissue.
Mice given the vaccine at a higher density were significantly less likely to develop colon tumors, suggesting that the platform could be adapted to target different cancer-specific proteins.
Another feature of the system is that the M13 virus can act as its own vaccine adjuvant, a substance that boosts the immune response. Its single-stranded DNA activates a signaling pathway called TLR9, which helps stimulate the body’s innate immune system.
By changing the genetic sequence of the virus, the researchers were also able to control this adjuvant activity. This may eliminate the need to add a separate immunostimulating ingredient to the vaccine.
A modular approach to cancer treatment
The platform’s modular design allows researchers to replace one antigen with another to target different types of tumors. This could ultimately support vaccines tailored to the specific molecular characteristics of an individual patient’s cancer.
The results build on the team’s previous work investigating the use of M13-based nanovaccines to treat established tumors in mice. In the latest study, however, the researchers primarily tested the vaccine’s ability to prevent tumor development.
The approach remains in the preclinical research stage. Further studies are needed to determine whether established cancers can be treated safely and effectively and whether the results can be translated to humans.
The research was published in the journal Advanced Healthcare Materials.
