Technion Study: Immunotherapy Drug Can Be Reduced To A Millionth Of Its Dose And Still Kill Cancer

JERUSALEM (VINnews) — Israeli scientists have made an immunotherapy drug effective with just a millionth of its original dose, according to a Technion study. The original drug fell at the last hurdle because regulators were concerned that the large dose could cause severe side effects. However the current technology uses a “Nano-Ghosts” platform, making it possible to reduce the drug dose a millionfold without reducing its efficacy in inhibiting melanomas.

The study, published in Advanced Functional Materials, was led by Prof. Marcelle Machluf, Dean of the Faculty, and PhD student Lior Levy.

This development is a significant breakthrough in the field of immunotherapy – an innovative medical approach that has become one of the most promising trends in cancer treatment. The approach is based on the ability of the body’s own immune system to destroy cancer cells. This system can do that more accurately and specifically than synthetic anti-cancer drugs. However, since the malignant tumor is heterogeneous and evasive, it can sometimes fool the immune system, and this is where science enters the picture, with new tools that help the immune system deal with this challenge.

At the core of this new development is a protein called TRAIL, which exists in the body’s immune system and knows how to induce apoptosis (programmed cell death) of cancer cells. In other words, it is a Tumor Necrosis Factor (TNF). Another advantage: it is selective, meaning it only affects cancer cells, a highly desirable feature in anti-cancer treatment. The application of TRAIL in immunotherapy has so far encountered various technical challenges, including the absorption of the protein in the body, its distribution (pharmacokinetics), and the fact that it does not survive for very long. This study offers a solution to these problems.

The study describes the preparation of “Nano-Ghosts” from cells that underwent genetic or metabolic manipulation and now carry the TRAIL protein. These cells, with Nano-Ghost targeting for cancer and with the TRAIL protein, can reach the cancer site and fight effectively while using one millionth the concentration of the active ingredient required without this system.

The “Nano-Ghost” platform, a unique concept developed by Prof. Machluf, is produced by emptying specific biological cells (mesenchymal stem cells) in a way that leaves only the cell membrane and reducing their size to a nanometer scale. Any drug can be inserted into the membrane and injected directly into the bloodstream. Because the body’s immune system treats nano-ghosts as natural cells, it delivers them to the affected site. They do not release the drug on the way, and therefore do not harm healthy tissue. They target the malignant tissue, where they deliver the drug into the tumor cells.

The study integrates the three aforementioned factors: the immunotherapy concept, the TRAIL protein, and the Nano-Ghost technology developed by Prof. Machluf. The result: a drug delivery system with the active protein on its outer layer, which allows reduction of the drug dosage by a factor of a million while maintaining the same treatment effect.
According to Prof. Machluf, “this integration turns the Nano-Ghost platform from a “taxi” that delivers the drug to the target into a “tank” that participates in the war. The integrated platform delivers the drug to the tumor and enables a significant reduction in drug dosage yet still does the job. We also showed that our method does not harm healthy cells.”

The technology was demonstrated on cells in the lab and on human cancer cells in mice. The researchers estimate that this new strategy, which was demonstrated in their study on a melanoma model, will also be effective on other types of cancer.

Machluf, dean of the Technion’s Faculty of Biotechnology and adviser to the NanoGhost startup, which is commercializing the technology, said the study was the strongest proof of concept yet for her invention.

“This delivers the drug to the tumor and enables a significant reduction in drug dosage yet still does the job, and also showed that our method does not harm healthy cells,” said Machluf.

“We have a totally different way to deliver a drug to cancer cells in a more targeted way, and this research indicates that we can actually use it to bring an excellent drug back to the market,” she said.