Researchers are developing a new way to boost the potency of cancer vaccines

A new way to dramatically increase the potency of almost any vaccine has been developed by researchers at the International Institute for Nanotechnology (IIN) at Northwestern University. Scientists have used chemistry and nanotechnology to alter the structural location of adjuvants and antigens on and in a nanoscale vaccine, dramatically increasing vaccine performance. The antigen targets the immune system and the adjuvant is a stimulator that increases the effectiveness of the antigen.

Scientists have used chemistry and nanotechnology to alter the structural location of adjuvants and antigens on and in a vaccine at the nanoscale, dramatically increasing vaccine performance. The antigen targets the immune system and the adjuvant is a stimulator that increases the effectiveness of the antigen.

The study will be published on January 30 in Nature Biomedical Engineering.

The work shows that the structure of the vaccine and not just the components is a critical factor in determining the vaccine efficiency. Where and how we position the antigens and adjuvant within a single architecture dramatically changes how the immune system recognizes and processes it.”

Chad A. Mirkin, IIN Director, Principal Investigator

Mirkin is also the George B. Rathmann Professor of Chemistry at Weinberg College of Arts and Sciences and Professor of Medicine at Northwestern University Feinberg School of Medicine.

This new emphasis on structure has the potential to improve the effectiveness of conventional cancer vaccines, which have not worked well in the past, Mirkin said.

Mirkin’s team has studied the effect of the vaccine structure in the context of seven different types of cancer to date, including triple negative breast cancer, HPV-induced cervical cancer, melanoma, colon cancer and prostate cancer to determine the most effective architecture to treat each disease.

Conventional vaccines take a mixer approach

With most conventional vaccines, the antigen and adjuvant are mixed together and injected into a patient. There is no control over the structure of the vaccine and therefore limited control over the trafficking and processing of vaccine components. Thus, there is no control over the effectiveness of the vaccine.

“A challenge with conventional vaccines is that from this jumbled hodgepodge, an immune cell can pick up 50 antigens and one adjuvant or one antigen and 50 adjuvants,” said the study author and former postdoctoral associate. from the North West, Michelle Teplensky, who is now an assistant. professor at Boston University. “But there has to be an optimal ratio of each that would maximize vaccine efficacy.”

Enter the SNAs (spherical nucleic acids), which are the structural platform -; invented and developed by Mirkin -; used in this new class of modular vaccines. SNAs allow scientists to determine exactly how much antigen and adjuvant is delivered to cells. SNAs also allow scientists to tailor how these vaccine components are presented and the speed at which they are processed. These structural considerations, which greatly impact vaccine efficacy, are largely ignored in conventional approaches.

Vaccines developed through “rational vaccinology” offer precise dosing for maximum efficacy

This approach to systematically controlling the locations of antigens and adjuvants in modular vaccine architectures was created by Mirkin, who coined the term rational vaccinology to describe it. It is based on the concept that the structural presentation of vaccine components is as important as the components themselves in driving efficacy.

“Vaccines developed through rational vaccinology deliver the precise dose of antigen and adjuvant to each immune cell, so they are all equally ready to attack cancer cells,” said Mirkin, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “If your immune cells are soldiers, a traditional vaccine leaves some of them unarmed; our vaccine arms them all with a powerful weapon to kill cancer. Which immune cell ‘soldiers’ do you want to attack your cancer cells?” Mirkin asked rhetorically.

Building an (even) better vaccine

The team developed a cancer vaccine that doubled the number of cancer antigen-specific T cells and increased the activation of these cells by 30% by reconfiguring the architecture of the vaccine to contain multiple targets to help the immune system find tumor cells.

The team studied differences in how two antigens were recognized by the immune system based on their placement –; on the core or the perimeter -; of the structure of the SNA. For an ANS with optimal placement, they could increase the immune response and how quickly the nanovaccine triggered the production of cytokines (a protein from immune cells) to stimulate T cells attacking cancer cells. The scientists also investigated how the different locations affected the immune system’s ability to remember the invader and whether the memory was long-term.

“Where and how we position the antigens and adjuvant within a single architecture dramatically changes how the immune system recognizes and processes it,” Mirkin said.

The strongest structure throws two punches to outsmart the cunning, mutating Tumor

The study data show that attaching two different antigens to an SNA comprising an adjuvant shell was the most powerful approach for a cancer vaccine structure. This led to a 30% 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 ANS.

These modified SNA nanostructures blocked tumor growth in several animal models.

“It’s remarkable,” Mirkin said. “When you change the placement of antigens in two vaccines that are almost compositionally identical, the benefit of tumor treatment is dramatically changed. One vaccine is potent and useful, while the other is much less effective .”

Many current cancer vaccines are designed to primarily activate cytotoxic T cells, a single defense against a cancer cell. Because tumor cells are always mutating, they can easily escape this surveillance by immune cells, quickly rendering the vaccine ineffective. The chances are higher that the T cell will recognize a mutating cancer cell if it has more means -; multiple antigens -; to recognize it.

“You need more than one type of T cell activated, so you can more easily attack a tumor cell,” Teplensky said. “The more the immune system has to attack tumors, the better. Vaccines consisting of multiple antigens targeting multiple types of immune cells are needed to induce enhanced and durable tumor remission.”

Another advantage of the rational vaccinology approach, especially when used with a nanostructure like an SNA, is that it is easy to modify the structure of a vaccine to tackle a different type of disease. Mirkin said they were simply swapping a peptide, an extract of a cancerous protein with a chemical handle that “clips” onto the structure, much like adding a new charm to a bracelet.

The path to the most effective vaccine for any type of cancer

“The collective significance of this work is that it lays the foundation for developing the most effective forms of vaccines for almost any type of cancer,” Teplensky said. “It’s about redefining the way we develop vaccines at all levels, including those against infectious diseases.”

In a previously published paper, Mirkin, Teplensky and their colleagues demonstrated the importance of vaccine structure for COVID-19 by creating vaccines that exhibited protective immunity in 100% of animals against deadly viral infection.

“Small changes in antigen placement on a vaccine dramatically increase cell-to-cell communication, crosstalk and cell synergy,” Mirkin said. “The developments made in this work pave the way for rethinking the design of vaccines against cancer and other diseases as a whole.”

Northwest Ph.D. candidate Michael Evangelopoulos is also the author of the article titled “Multi-Antigen Spherical Nucleic acid cancer vaccines.”

Founded in 2000 as an umbrella organization to merge and foster nanotechnology efforts, the IIN represents and brings together more than $1 billion in nanotechnology research, educational programs, and supporting infrastructure.

This study is based on work supported by the Polsky Urologic Cancer Institute at Northwestern University’s Robert H. Lurie Comprehensive Cancer Center at Northwestern Memorial Hospital, Edward Bachrach and the National Cancer Institute of the National Institutes of Health (R01CA208783, R01CA257926 and P50CA221747 ). Teplensky also received support from Northwestern University’s Cancer Nanotechnology Training Program Award (T32CA186897). Evangelopoulos was partially supported by the Dr. John N. Nicholson Fellowship and the Alexander S. Onassis Charitable Foundation.