Researchers at Binghamton University have developed a new approach to mRNA cancer vaccines that may improve the immune system's ability to target and destroy cancer cells. The research, led by Associate Professor Yuan Wan from the Department of Biomedical Engineering at the Thomas J. Watson College of Engineering and Applied Science, was published in the journal Theranostics.
The new method uses chimeric nanobodies with lipid tails engineered in cell factories. These nanobodies self-assemble with lipids, encapsulating mRNA to form nanoparticles that display nanobodies on their surface. This design allows the nanoparticles to specifically attach to tumors that overexpress human epidermal growth factor receptor 2 (HER2), a characteristic found in many cancer cells.
"We train the immune system using markers from the tumor. When cancer cells with that marker appear, natural immune responses can recognize and destroy them," said Wan.
Unlike traditional vaccines that use dead or weakened pathogens, these mRNA vaccines instruct tumor cells to produce a protein similar to one found on invaders such as viruses. Specifically, spike proteins from SARS-CoV-2 are expressed on cancer cell walls, prompting an immune response against those cells.
"In the last 50 years, scientists didn't have very good progress with cancer vaccines because tumors keep evolving - each one will, probably, develop differently," Wan explained. "If you use a vaccine against a tumor marker for treatment but the tumor develops in a different way, the treatment becomes useless. In this newest strategy, scientists use a vaccine to force the cancer cells to show unique surface proteins. This acts like a switch, activating the immune system so it can recognize and specifically wipe out the tumor cells."
Wan described how these nanoparticles work: "When they bind to the tumor surface, they get into the tumor and release the mRNA that will express the spike proteins. These spike proteins effectively stimulate a robust immune response in the body. Ultimately, the activated immune system will specifically recognize these spike protein-marked tumors and kill them.
"Thanks to the COVID-19 pandemic, most of us already have immune memory for this specific spike protein in our bodies. So, if a tumor cell is made to express that same spike protein, the body's immune system says, 'Wait a minute - this looks like a virus infection again!' The immune system then naturally and immediately rushes in to destroy these tumor cells, treating them just like they were virus-infected invaders."
An additional benefit is that these nanoparticles do not use polyethylene glycol (PEG), which has been associated with adverse reactions in some patients. By altering which nanobody is used on their surface, researchers can adapt these nanoparticles for various types of tumors.
Testing so far has shown promising results for targeting cancer cells and inducing an immune response; however, further research is needed before human trials can begin. Scaling up production methods for larger quantities of these targeted nanoparticles is also required.
"These mRNA treatments could be the key to many pervasive medical problems, such as infectious diseases, oncology and immune modulation," said Wan. "They could revolutionize preventive and therapeutic medicine."
Other contributors include Binghamton postdoctoral researcher Md. Mofizur Rahman; Chuandong Zhu and Lixue Wang from Nanjing University of Chinese Medicine; Jing Wang from Nanjing University Medical School; and Yun Zhang from Nanjing Regenecore Biotech Co.
