Vaccine design can dramatically improve cancer immunotherapies

As for the effectiveness of nanotherapeutic vaccines, form is important.

A team from Northwestern University has been studying a set of spherical nucleic acids (SNAs) to determine their potential to stimulate immune responses that suppress cancer. After comparing a series of vaccines of identical composition but different structure, testing them on several animal models, the researchers found that the structure of ANS in one vaccine greatly outperformed the others, ranging from ineffective to almost curative.

Higher-structure vaccines completely eliminated tumors in 30% of animals and improved overall survival following cancer. The vaccine also protected animals from re-emerging tumors.

"This observation shows the importance of the chemical structure and three-dimensional presentation of the active components in vaccine design," said Chad A. Mirkin of the North West, who led the study. "This information will help us to rationally design SNA vaccines capable of generating the strongest anti-cancer immune responses possible.A clear design strategy will also accelerate the development of vaccines for many types of cancer and potentially other diseases. "

The study will be published online during the week of May 6 in the newspaper Proceedings of the National Academy of Sciences.

Mirkin is Professor of Chemistry George B. Rathmann at the Weinberg College of Arts and Sciences, in the Northwest, and Director of the International Institute of Nanotechnology. He co-directed the study with Bin Zhang, Professor of Medicine and Microbiology-Immunology at the Feinberg School of Medicine at Northwestern University, and Andrew Lee, Research Assistant Professor in Chemical and Biological Engineering at McCormick School. of Engineering Northwestern.

The anti-cancer immunotherapies artificially stimulate the patient's immune system so that it detects and attacks the disease. Until now, new immunotherapies, called checkpoint inhibitors, work by unlocking immune responses suppressed by tumors. But they are only effective in certain types of cancer and in a fraction of patients.

"Another potentially more powerful approach is to increase and strengthen immune responses with therapeutic vaccines," Lee said. "However, this approach has required breakthroughs in vaccine design to exploit its full potential in the treatment of cancer in the clinic."

The development of SCN could be the breakthrough expected by people. Invented by Mirkin, SCNs are synthetic, rather than linear, global forms of DNA and RNA that surround a nucleus of nanoparticles. From a diameter of about 50 nanometers, these tiny structures possess the ability to enter cells, including immune cells, for targeted treatment delivery.

In the study, the North West team compared the SCNs having different structures but the same peptides, DNA and other general components. All vaccines included an antigen (a substance recognized and targeted by an immune response) and an adjuvant (a substance that enhances the body's immune response to the antigen). In this case, the DNA is the adjuvant and the peptide is the antigen.

The only thing that changed in each vaccine was the position of the peptide antigen, which was either lodged in the nucleus of the SNA, interspersed with DNA or attached to the DNA. These changes have led to major differences in how the immune system recognizes and processes molecular signals, ultimately affecting the quality of the immune response generated by the vaccine. In the study, the peptide peg interspersed with DNA gave the best results.

"The study shows that SNAs and our ability to refine SNA structures can dramatically improve the anti-tumor immune response," Zhang said. "This sounds promising in our ability to improve vaccine performance and possibly use it in patient care."