A toxin which upon direct administration to cancerous cells induces suicide was discovered by the researchers from Tel Aviv University, Israel. The researchers successfully encoded a bacterial toxin into mRNA (messenger RNA) molecules and when these mmRNA (modified mRNA) molecules were unfolded by the cancer cells’ machinery, the resultant product was a toxin which ultimately kills the cancerous cells proven in animal models.
The research was led by Professor Dan Peer and PhD student Yasmin Granot-Matok. The success of the research was attributed to 50%. Professor Peer compared their mmRNA-encoding bacterial toxin to a Trojan horse exposed to a cancerous environment.
The Toxin Manipulation
The researchers here used a toxin produced by the bacteria Pseudomonas aeruginosa– exotoxin A. The mRNA-based approach uses the encoding of exotoxin-A in lipid nanoparticles (LNPs). These LNPs were then directly administered into mice with B16-melanoma tumors. This was an effort to enhance a strategy for toxin-based anti-tumor therapy, characterized by improved safety, reduced immune response, and sustained high effectiveness.
Image Source: Centers for Disease Control and Prevention
The cancer treatment used by professionals and which is widely used around the world is chemotherapy. In chemotherapy, small molecules are deployed through the bloodstream to subdue cancerous cells. It has its own vast array of limitations- it is often reported to attack healthy cells of the body and is coupled with additional side effects of hair loss, fatigue, anemia amongst many others.
The aim of the scientists in the study ‘Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors’ was to transport secure mRNA molecules containing instructions for a bacterial toxin enclosed in LNPS directly to the cancer cells. This approach would prompt the cancer cells to generate the toxic protein internally, leading to their own demise.
The results after the injection of the very first dose resulted in clearance of 44-60% of the cancerous cells. The researchers emphasized on the fact that the cancerous cells will not develop resistance towards this new break-through because even if they did, a new natural toxin can be employed for the same.
Other Widely Popular Toxins
A most commonly known bacterial toxin is Botulinum toxin secreted by Clostridium botulinum which is used in cosmetic treatments such as Botox. Although Botulinum toxin is considered as a potent neurotoxin, it is also used in therapeutics as a treatment for chronic migraine, cervical dystonia, detrusor overactivity, and spastic disorders.
According to Professor Peer, this prolific approach can potentially utilize the toxins secreted by numerous anaerobic bacteria as well, particularly those residing in soil environments. He further extended that it is highly likely that a wide range of these toxins can be employed in conjunction with the new approach.
A Limitation of the Study
The therapeutic time frame is reported as a restraint which resulted in tumor-relapse in advanced stages of experimental research. The scientists say that this might be due to a highly competitive nature and rapid growth rate of the B16 myeloma cells. The possible deduction scientists made from this was because of the intratumoral injections facing intrinsic challenges in reaching a large portion of tumor cells during the late stages of tumor growth.
In their future research, the scientists intend to investigate the potential of the mmRNA-LNPs based technique to achieve a more even and targeted distribution in the tumor cells through the bloodstream. This approach is expected to enhance the therapeutic effectiveness of the technology in future. The researchers plan to explore the effects of the technique on additional tumor models to validate their research.