Scientists establish blueprint to redevelop cancer vaccines
The blueprint has been established for redeveloping all vaccines, including those for infectious diseases and cancers.
Researchers from the International Institute for Nanotechnology at Northwestern University have made a breakthrough by developing a new method to increase the potency of almost any vaccine, according to a press release.
How did they do it? Chemistry and nanotechnology were used to change the structural location of adjuvants (a stimulator that increases the effectiveness of the antigen) and antigens (targets the immune system) on and within a nanoscale vaccine, thereby highly increasing vaccine performance.
The blueprint from the study can now redevelop all vaccines — including those for infectious diseases like COVID-19 — and improve outcomes for seven different types of cancer.
“The work shows that vaccine structure and not just the components are a critical factor in determining vaccine efficacy,” lead investigator Chad A. Mirkin, director of the IIN, said in the press release.
“Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it.”
The team focused on the vaccine structure
Mirkan and team emphasize the vaccine structure, which they believe has the potential to improve the effectiveness of conventional cancer vaccines.
So far, Mirkin’s team has studied this effect in seven different types of cancer, including triple-negative breast cancer, papillomavirus-induced cervical cancer, melanoma, colon cancer, and prostate cancer to “determine the most effective architecture to treat each disease”.
“Small changes in antigen placement on a vaccine significantly elevate cell-to-cell communication, cross-talk, and cell synergy,” Mirkin said. “The developments made in this work provide a path forward to rethinking the design of vaccines for cancer and other diseases as a whole.”
With conventional vaccines, the antigen and adjuvant are combined and injected into a patient. This results in zero control over the vaccine structure.
“A challenge with conventional vaccines is that out of that blended mish-mosh, an immune cell might pick up 50 antigens and one adjuvant or one antigen and 50 adjuvants,” said study author and former Northwestern postdoctoral associate Michelle Teplensky, who is now an assistant professor at Boston University. “But there must be an optimum ratio of each that would maximize the vaccine’s effectiveness.”
Rational vaccinology to control antigen and adjuvant locations
To tackle the problem, Mirkan invented spherical nucleic acids (SNAs), a structural platform used in this new class of modular vaccines. SNAs permit scientists to zero in on the exact number of antigens and adjuvants delivered to cells. The platform also helps scientists tailor and process the vaccine components.
The team developed a new cancer vaccine that “doubled the number of cancer antigen-specific T cells and increased the activation of these cells by 30 percent by reconfiguring the architecture of the vaccine to contain multiple targets to help the immune system find tumor cells,” according to the release.
The scientists checked the difference in how well two antigens were recognized by the immune system based on their placement in the SNA structure.
“Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it,” Mirkin said.
Mirkan also coined the term ‘rational vaccinology’ to describe the approach to systematically control antigen and adjuvant locations within modular vaccine architectures. “Vaccines developed through rational vaccinology deliver the precise dose of antigen and adjuvant to every immune cell, so they are all equally primed to attack cancer cells,” he said.
The engineered vaccine stalled tumor growth in multiple animal models
The study data eventually revealed that attaching two different antigens to an SNA with a shell of adjuvant was the most powerful approach for a cancer vaccine structure. It led to a 30 percent increase in antigen-specific T-cell activation and doubled the number of proliferating T cells compared to a structure in which the same two antigens were attached to two separate SNAs.
These engineered SNA nanostructures were found to stall tumor growth in multiple animal models.
“It is remarkable,” Mirkin said. “When altering the placement of antigens in two vaccines that are nearly identical from a compositional standpoint, the treatment benefit against tumors is dramatically changed. One vaccine is potent and useful, while the other is much less effective.”
“The collective importance of this work is that it lays the foundation for developing the most effective forms of vaccine for almost any type of cancer,” Teplensky said. “It is about redefining how we develop vaccines across the board, including ones for infectious diseases.”
The study is published in Nature Biomedical Engineering.
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