Tel Aviv University researchers have for the first time used a single injection into the tumor bed of animals with melanoma to cause 44% to 60% of the cancer cells to disappear completely and permanently. They maintain that “with the new technology, we induced the cancer cells to produce the toxic protein that eventually killed them.”
The TAU researchers encoded a toxin produced by bacteria into mRNA (messenger RNA) molecules and delivered these particles directly to cancer cells, causing the cells to produce the toxin that eventually killed them at an impressive success rate.
The study they called “groundbreaking” was led by doctoral student Yasmin Granot-Matok and Prof. Dan Peer, a pioneer in the development of RNA therapeutics and head of the Nanomedicine Laboratory at TAU’s Shmunis School of Biomedicine and Cancer Research, who also serves as the university’s vice president for research and development.
The study’s results were published in Theranostics under the title “Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors.”
New methods to stop cancer cell growth
They said that cancer therapies have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. “Many bacteria secrete toxins,” Peer explained.
“The most famous of these is probably the botulinum toxin injected in botox treatments. Another classic treatment technique is chemotherapy, involving the delivery of small molecules through the bloodstream to effectively kill cancer cells. But chemotherapy has a major downside in that it is not selective and kills healthy cells as well as cancer cells. Our idea was to deliver safe mRNA molecules encoded for a bacterial toxin directly to the cancer cells – inducing them to produce the toxic protein that would later kill them. It’s like placing a Trojan horse inside the cancer cell.”
First, the research team encoded the genetic info of the toxic protein produced by bacteria of the pseudomonas family into mRNA molecules (resembling the procedure in which genetic info of COVID-19’s ‘spike’ protein was encoded into mRNA molecules to create the vaccine).
The mRNA molecules were then packaged in lipid nanoparticles developed in Peer’s lab and coated with antibodies to make sure that the instructions for producing the toxin would reach the targeted cancer cells. The particles were injected into the tumors of animal models with melanoma skin cancer, and after just one shot, an average of half of the cancer cells vanished.
“In our study, the cancer cell produced the toxic protein that eventually killed it,” Peer said. “We used pseudomonas bacteria and the melanoma cancer, but this was only a matter of convenience. Many anaerobic bacteria (that exist without free oxygen) – especially those that live in the ground – secrete toxins, and most of these can probably be used with our method."
“This is our ‘recipe,’ and we know how to deliver it directly to the target cells with our nanoparticles. When the cancer cell reads the ‘recipe’ at the other end, it starts to produce the toxin as if it were the bacteria itself – and this self-produced toxin eventually kills it. So, with a simple injection to the tumor bed, we can cause cancer cells to ‘commit suicide’ without damaging healthy cells. In addition, cancer cells can’t develop resistance to our technology, as often happens with chemotherapy, because we can always use a different natural toxin.”