Nov 28, 2021

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There are more than 100 kinds of cancer that can attack human organs, and mankind is still far from obliterating them, but the battle against malignancies is nevertheless progressing and offering hope. Now, a new medical technology developed at the Technion-Israel Institute of Technology in Haifa has been found to improve the effect of anti-cancer drugs, makes it possible to reduce the drug dose a million-fold without reducing its efficacy

The technology, based on the “Nano-Ghosts” platform, has already proven successful in treating pancreatic, lung, breast, prostate, and brain cancer in mice. Nano-Ghost is a drug-delivery technology that uses adult stem cells to transport medicine directly to the tumor site. 

The researchers in the Technion’s Faculty of Biotechnology and Food Engineering were led by led by Prof. Marcelle Machluf, dean of the faculty, and doctoral student Lior Levy. Their study was published in the journal Advanced Functional Materials under the title “TRAIL-Coated, Genetically Engineered Immunotherapeutic Nano-Ghosts Vesicles Target Human Melanoma-Avoiding the Need for High Effective Therapeutic Concentration of TRAIL.” 

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. The Technion system can do that more accurately and specifically than synthetic anti-cancer drugs, but 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 tumor necrosis factor (TNF) protein called TRAIL, which exists in the body’s immune system and knows how to induce apoptosis (programmed cell death) of cancer cells. 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. 

A schematic description of preparing 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 (courtesy: doron Shaham-marcus (Technion))

It is based on original technology developed by Machluf and her team for 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 thus they do not harm healthy tissue. They target the malignant tissue, where they deliver the drug into the tumor cells.


The result is a drug-delivery system with the active protein on its outer layer that allows reduction of the drug dosage by a factor of a million while maintaining the same treatment effect. “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,” explained Machluf. 


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