Researchers develop new ways to boost potency of cancer vaccines

A new method has been developed by researchers at the International Institute of Nanotechnology (IIN) at Northwestern University to significantly increase the efficacy of nearly any vaccine. Scientists are using chemistry and nanotechnology to change the structural position of adjuvants, antigen Significantly improve vaccine performance on and within nanoscale vaccines. Antigens target the immune system, and adjuvants are stimulants that increase the effectiveness of antigens.

Scientists have used chemistry and nanotechnology to alter the structural location of adjuvants and antigens on and within nanoscale vaccines, greatly enhancing vaccine performance. Antigens target the immune system, and adjuvants are stimulants that increase the effectiveness of antigens.

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

This study shows that the structure of the vaccine, not just the ingredients, is a key factor in determining the vaccine. EffectivenessWhere and how you place antigens and adjuvants within a single architecture significantly changes how the immune system recognizes and processes them. “

Chad A. Mirkin, IIN Director, Principal Investigator

Markin is also the George B. Rathman Professor of Chemistry at Weinberg College of Arts and Sciences and Professor of Medicine at Northwestern University’s Feinberg School of Medicine.

This new emphasis on structure has the potential to improve the effectiveness of traditional cancer vaccines that have historically failed, Mirkin said.

Merkin’s team has so far studied the impact of vaccine constructs in the context of seven different types of cancer, including triple-negative breast cancer, papillomavirus-induced cervical cancer, melanoma, colon cancer, and prostate cancer. We determined the most effective architecture for treating each disease.

Traditional vaccines take a blender approach

Most conventional vaccines mix the antigen with an adjuvant and inject it into the patient. Vaccine structure cannot be controlled, resulting in limited control over the transport and processing of vaccine components. Therefore, it is not possible to control the effectiveness of the vaccine.

“The challenge with conventional vaccines is that immune cells may pick up 50 antigens and 1 adjuvant, or 1 antigen and 50 adjuvants, from a mixed mishmosh,” said the study author, Michelle Teprenski, a former Northwestern University postdoctoral fellow who is now an assistant, said. Professor at Boston University. “But to maximize vaccine efficacy, we need an optimal ratio of each.”

Enter the structural platform SNA (Spherical Nucleic Acid). Invented and developed by Markin -; used in this new class of modular vaccines. SNA allows scientists to precisely identify the number of antigens and adjuvants that have been delivered to cells. SNA also allows scientists to tailor how these vaccine components are presented and the speed at which they are processed. Such structural considerations, which greatly affect vaccine efficacy, are largely ignored by conventional approaches.

Vaccines developed by ‘rational vaccinology’ provide precise dosages for maximum efficacy

This approach of systematically controlling the location of antigens and adjuvants within a modular vaccine architecture was created by Merkin, 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 promoting efficacy.

“Vaccines developed by rational vaccinology deliver precise doses of antigens and adjuvants to all immune cells, so that all immune cells are equally primed to attack cancer cells,” said the university. “If your immune cells are soldiers, conventional vaccines will leave those unarmed. Our vaccines will arm them all with powerful weapons that kill cancer. “Do you want soldiers to attack your cancer cells?” Merkin asked rhetorically.

(More) Building better vaccines

By reconfiguring the vaccine’s architecture to include multiple targets to help the immune system find tumor cells, the team doubled the number of cancer antigen-specific T cells and increased the activity of these cells. developed a cancer vaccine that increases cytotoxicity by 30%.

The team investigated differences in the extent to which the two antigens are recognized by the immune system depending on their placement. core or perimeter -; of the SNA structure. By optimally positioning the SNA to increase the immune response, we will see how quickly the nanovaccine can trigger the production of cytokines (immune cell proteins) to boost her T cells to attack the cancer cells. You can find out. Scientists have also studied how different placements affect the immune system’s ability to remember intruders, and whether memory is long-term.

“Where and how you place an antigen and adjuvant within a single architecture significantly changes how the immune system recognizes and processes it,” Mirkin said.

The most powerful structure throws two punches to outwit the cunning mutant tumor

Research data indicate that conjugating two different antigens to SNA containing an adjuvant shell is the most powerful approach to cancer vaccine construction. This resulted in a 30% increase in antigen-specific T cell activation and doubled the number of proliferating T cells compared to the same two antigens bound to two separate SNA constructs .

These engineered SNA nanostructures halted tumor growth in multiple animal models.

“It’s amazing,” Merkin said. “If you change the arrangement of the antigens in the two vaccines, which are almost identical from a compositional point of view, you can dramatically change their therapeutic effect on tumors. is much less effective.”

Many current cancer vaccines are primarily designed to activate cytotoxic T cells and offer only one protection against cancer cells. Because tumor cells are constantly mutating, they easily escape this immune cell surveillance, rendering vaccines ineffective quickly. The more pathways, the more likely T cells will recognize mutant cancer cells. multiple antigens -; recognize it;

“To make it easier to attack tumor cells, we need to activate multiple types of T cells,” Dr. Teplensky said. “The more cell types the immune system needs to track a tumor, the more effective it is. A multi-antigen vaccine that targets multiple immune cell types can lead to enhanced and long-lasting tumor remission. necessary to induce

Another advantage of a rational vaccinology approach, especially with nanostructures like SNA, is that it becomes easier to alter the structure of vaccines to target different types of diseases. According to Mirkin, they’ve simply replaced the peptides, fragments of cancer proteins with chemical handles that “clip” into the structure, much like adding new charm to bracelets.

Path to the most effective vaccine against all types of cancer

“The overall significance of this study is to lay the groundwork for developing the most effective vaccines against nearly all types of cancer,” said Dr. Teplensky. “It’s about redefining how we develop vaccines across the board, including vaccines for infectious diseases.”

In a previously published paper, Mirkin, Teplensky, and colleagues highlight the importance of vaccine construction for COVID-19 by creating a vaccine that exhibits protective immunity in 100% of animals against lethal viral infection. Proven.

“Even a small change in antigen placement in a vaccine can greatly improve cell-to-cell communication, cross-talk and cell synergy,” Mirkin said. “The developments made in this study provide an avenue for rethinking vaccine design across cancer and other diseases.”

Northwestern PhD Candidate Michael Evangelopoulos is also the author of a paper entitled “Multi-antigen spheroids” nucleic acid cancer vaccine. “

Founded in 2000 as an umbrella organization to integrate and advance nanotechnology efforts, IIN represents and integrates more than $1 billion in nanotechnology research, educational programs, and supporting infrastructure.

This study was supported by Polsky Urological Cancer Institute, Edward Bachrach, Northwestern University’s Robert H. Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, and the National Cancer Institute, National Institutes of Health (R01CA208783, R01CA257926). , and P50CA221747). ). Teplensky was also supported by the Northwestern University Cancer Nanotechnology Training Program Award (T32CA186897). Evangelopoulos was supported in part by a Dr. John N. Nicholson Fellowship and the Alexander S. Onassis Public Interest Foundation.