Binghamton University-led researchers have designed tumor-seeking mRNA nanoparticles that use COVID-era immune memory to help the body recognize and destroy cancer cells. The approach could make future cancer vaccines more precise and easier on patients than chemotherapy or radiation.
For decades, doctors have relied on chemotherapy and radiation to fight cancer, even though those treatments can damage healthy cells and cause harsh side effects. Now, researchers led by biomedical engineer Yuan Wan from Binghamton University say a new way of delivering mRNA cancer vaccines could help the body do the job more precisely on its own.
Building on lessons from COVID-19 vaccines, the researchers have developed tiny, tumor-targeting particles that deliver mRNA directly to cancer cells. Their work, published in the journal Theranostics, suggests a strategy that could one day make cancer vaccines more effective and easier to tailor to different tumors.
Wan, an associate professor in Binghamton’s Thomas J. Watson College of Engineering and Applied Science, studies how to get cancer drugs and vaccines exactly where they are needed. He said the goal is to turn the immune system into a smart, selective weapon.
“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,” Wan said in a news release.
Traditional cancer vaccines have struggled because tumors are constantly changing. As cancer cells grow and mutate, the proteins on their surfaces can shift, making it hard for a single vaccine design to keep up.
“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 added. “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 new approach uses mRNA, the same type of genetic material used in many COVID-19 vaccines. Instead of teaching the body to recognize a virus, however, the Binghamton-led team designed mRNA that tells cancer cells to make a familiar viral protein on their own surfaces.
To deliver that mRNA, the researchers created chimeric nanobodies — small, antibody-like molecules — with lipid tails. In cell factories, these nanobodies self-assemble with fats to form mRNA-lipid nanoparticles. The result is a tiny capsule with mRNA inside and nanobodies sticking out from the surface.
Those surface nanobodies are engineered to seek out and latch onto tumors that overproduce a protein called human epidermal growth factor receptor 2, or HER2. HER2 is a well-known marker that is overexpressed in several types of cancer.
Once the nanoparticles arrive at a HER2-positive tumor, they go to work.
“When they bind to the tumor surface, they get into the tumor and release the mRNA that will express the spike proteins,” added Wan.
The spike proteins in this case are modeled on the SARS-CoV-2 spike — the same viral feature that COVID-19 vaccines target. When tumor cells start displaying that spike on their surfaces, the immune system sees something it already knows is dangerous.
“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,” Wan added.
Because so many people now have immune memory against the SARS-CoV-2 spike protein, this tactic could give the body a head start. The immune system does not have to learn a new cancer-specific marker from scratch; it can reuse its existing defenses to attack tumor cells that suddenly look like virus-infected invaders.
The design also addresses a safety concern that has emerged with some nanoparticle-based medicines. Many current formulations rely on polyethylene glycol, or PEG, a chemical that helps stabilize particles but can cause allergic or other adverse reactions in some patients.
In the new system, the nanoparticles are built without PEG. The nanobody component can also be swapped out, allowing scientists to retarget the particles to different tumor types that express other surface markers. That flexibility could make it easier to adapt the platform across a wide range of cancers.
So far, Wan and his team have tested how well the spike protein-based strategy triggers immune responses against targeted cancer cells, using human tissue samples in experimental studies. The early results are promising, but the researchers emphasize that the work is still in its preclinical stages.
Before any human trials can begin, the team needs to refine the technology and figure out how to manufacture the specialized nanoparticles at scale. Right now, they can only produce small batches in the lab, which is not enough for widespread testing or clinical use.
Scaling up is a common hurdle for cutting-edge therapies. Manufacturing must be consistent, safe and cost-effective, especially for complex biological products like mRNA-lipid nanoparticles. The researchers are now focused on developing methods that could support larger-scale production while preserving the particles’ targeting ability.
Beyond cancer, Wan sees potential for this kind of mRNA delivery system to play a role in many areas of medicine. mRNA therapies can, in principle, instruct cells to make almost any protein, opening the door to new treatments for infectious diseases, immune disorders and more.
If the tumor-targeting strategy pans out, it could mark a shift in how doctors think about cancer vaccines — from chasing ever-changing tumor markers to forcing tumors to reveal a consistent, recognizable signal.
The work also highlights how quickly the science behind COVID-19 vaccines is being repurposed. In just a few years, the same basic tools that helped control a global pandemic are being reimagined as precision weapons against one of the world’s deadliest diseases.
For now, the Binghamton-led team’s findings offer a glimpse of what future cancer care might look like: treatments that are less toxic than chemotherapy, more adaptable than traditional vaccines and powered by the body’s own immune memory.
Source: Binghamton University