No matter where cancer cells grow in the human body, they are a threat to our health and our lives. But instead of treating them with chemotherapy or radiation - which have undesirable side effects - what if we could train our own immune systems to kill the rogue cells?
That's the idea behind mRNA cancer vaccines, which build on science learned from COVID-19 vaccines to address an even larger health concern.
In a recent issue of the academic journal Theranostics, Binghamton University Associate Professor Yuan Wan and his collaborators outline a better way to target mRNA treatments. It builds on Wan's work over the past five years to develop a better delivery method for chemotherapy medications.
"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, a faculty member at the Thomas J. Watson College of Engineering and Applied Science's Department of Biomedical Engineering.
Instead of a dead or weakened version of the virus or bacteria, mRNA vaccines tell tumor cells to manufacture a protein that resembles something an unwanted invader would produce. Spike proteins from the SARS-CoV-2 virus grow on cancer cell walls and trigger an immune response in the human body against cancer 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 said. "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."
The research team developed chimeric nanobodies featuring lipid tails engineered in cell factories. These nanobodies self-assemble with lipids, encapsulating mRNA to form mRNA-lipid nanoparticles with protruding nanobodies on the surface. These surface nanobodies enable the nanoparticles to specifically attach to tumors that overexpress human epidermal growth factor receptor 2 (HER2), a key trait of many cancer cells.
"When they bind to the tumor surface, they get into the tumor and release the mRNA that will express the spike proteins," Wan said. "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."
Another advantage of this new research is that these nanoparticles do not rely on polyethylene glycol (PEG), a common bioengineering chemical that can lead to adverse reactions in patients. By changing the nanobody part, the targeted nanoparticles can be adapted for a wide range of tumors.
Wan and his team tested the spike protein-induced immune response to the targeted cancer cells and saw promising results, but further investigation and refining are needed before human medical trials. The next step is to develop methods for larger-scale manufacturing of these tumor-targeting mRNA-lipid nanoparticles, because right now, they are produced only in small batches.
"These mRNA treatments could be the key to many pervasive medical problems, such as infectious diseases, oncology and immune modulation," Wan said. "They could revolutionize preventive and therapeutic medicine."
Also contributing to the Theranostics paper are Binghamton postdoctoral researcher Md. Mofizur Rahman; Chuandong Zhu and Lixue Wang from the Nanjing University of Chinese Medicine; Jing Wang from Nanjing University Medical School; and Yun Zhang from Nanjing Regenecore Biotech Co.
