Researchers induce cancer cells to ‘commit suicide’ by a

A new approach to fighting cancer:

Researchers induce cancer cells to ‘commit suicide’

with self-produced bacterial toxins

• Impressive results: After one injection into the tumor bed in animal models with melanoma, 44–60% of cancer cells disappear completely and permanently.
• The researchers: “With our new technology we make cancer cells produce toxic proteins that eventually kill them.”

For a world first: researchers at Tel Aviv University encode a toxin produced by bacteria into mRNA (messenger RNA) molecules and deliver these particles directly to cancer cells, causing the cells to produce the toxin – which eventually kills them with a success rate of 50%. This groundbreaking study was led by PhD student Yasmin Granot-Matok and Prof. Dan Peer, a pioneer in the development of RNA therapy and Head of the Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research, who also serves as TAU’s VP R&D. The results of the study were published in Theranostika.

Prof. Peer explains: “Many bacteria secrete toxins. The most well-known is probably the botulinum toxin that is injected in the Botox treatment. Another classic treatment technique is chemotherapy, which involves sending small molecules through the bloodstream to effectively kill cancer cells. However, chemotherapy has a major drawback: it is not selective, and it also kills healthy cells. Our idea is to deliver a safe mRNA molecule that encodes for a bacterial toxin directly to the cancer cells – encouraging these cells to actually produce toxic proteins that in turn kill them. It’s like putting a Trojan horse inside a cancer cell.”

First, the research team encoded the genetic information of a toxic protein produced by bacteria of the pseudomonas family into an mRNA molecule (resembling the procedure in which the genetic info of a COVID-19 ‘spike’ protein is encoded into an mRNA molecule to make a vaccine). The mRNA molecule is then packaged in lipid nanoparticles developed in Prof.’s laboratory. Peer and coated with antibodies – to ensure that the instructions for producing the toxin will reach its target, which is the cancer cell. The particles were injected into the tumor of an animal model with melanoma skin cancer. After one injection, 44-60% of cancer cells disappear.

“In our study, cancer cells produce toxic proteins that eventually kill them,” said Prof. Peers. “We use pseudomonas bacteria and melanoma cancer, but it’s just a matter of convenience. Many anaerobic bacteria, especially those that live in soil, secrete toxins, and most of these toxins are probably usable by our method. This is our ‘recipe’, and we know how to deliver it directly to the target cell with our nanoparticles. When the cancer cell reads the ‘recipe’ on the other end, it starts producing the toxin as if it were the bacteria itself and this self-produced toxin eventually kills it. So, with a simple injection into a tumor, we can cause cancer cells to ‘commit themselves’, without harming healthy cells. Plus, cancer cells can’t develop resistance to our technology like chemotherapy often does – because we can always use a different natural toxin.”

Other contributors to this research include: Dr. Assaf Ezra, Dr. Srinivas Ramishetti, Dr. Preeti SharmaDr. Gonna Somu Naidu and Prof. Itai Benhar, Head of the Antibody Engineering Lab at the Shmunis School of Biomedicine and Cancer Research at TAU. This study was funded by the Shmunis Family Foundation for Biomedicine and Cancer Research.

Link to article:

https://www.thno.org/v13p3497.htm