Israeli scientists have developed a universal treatment against cancer

https://www.jpost.com/HEALTH-SCIENCE/A-cure-for-cancer-Israeli-scientists-say-they-think-they-found-one-578939
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A small group of Israeli scientists believe that they have found the first universal treatment against cancer.
"We believe that in a year we will offer a universal treatment against cancer," said Dan Aridor about a new treatment developed by his company, Accelerated Evolution Biotechnologies Ltd. (AEBi), which was founded in 2000 in the ITEK incubator. AEBi has developed a SoAP platform that provides functionality for solving very complex problems.
“Our cancer treatment will be effective from day one, will last several weeks and will not have side effects, other than minimal ones, at a much lower price than many other types of treatment on the market,” said Aridor. "We plan and license our solution, and release it ourselves."

It sounds fantastic, especially considering that, according to reports from the International Agency for Research on Cancer, about 18.1 million new cases of cancer are diagnosed worldwide every year. In addition, every sixth death in the world comes from cancer, which makes it the second leading cause of death (second only to cardiovascular diseases).

Aridor, chairman of the board of directors of AEBi, and CEO Ilan Morad say that their treatment, which they call MuTaTo (multi-target toxi), is similar in scope to the invention of antibiotics - a breakthrough technology of the highest level.

Their revolutionary anticancer drug is based on SoAP technology, which belongs to the phage display technology group.. This involves introducing a DNA that encodes a protein, such as an antibody, into a bacteriophage, a virus that infects bacteria. This protein then appears on the surface of the phage. Researchers can use the resulting proteins to screen for interactions with other proteins, DNA sequences and small molecules.

In 2018, a group of scientists received the Nobel Prize for their work on phage display in the directional evolution of new proteins, in particular, for the development of antibody preparations.

AEBi does something similar, but with peptides. According to Morad, peptides have several advantages over antibodies, because they are smaller, cheaper and easier to obtain and control.

When the company was just starting, Morad said: "We did what everyone else did, trying to find personalized new peptides for specific types of cancer." But shortly thereafter, Morad and his colleague, Dr. Hanan Yitzchaki, decided that they wanted to do something more.

To get started, they needed to find out why other drugs that kill cancer do not work or eventually fail. And they found a way to counter this effect.

As a rule, most anticancer drugs attack a specific target on or inside a cancer cell, he explained. Target inhibition usually affects the physiological pathway of cancer. Mutations in targets — or downstream in their physiological pathways — can remove targets from the cancerous nature of the cell, and therefore the drug attacking it becomes ineffective.

In contrast, MuTaTo uses a combination of several cancer-targeted peptides in combination with a strong peptide toxin that would specifically kill cancer cells. According to Morad, using at least three peptides and a strong toxin, “we have seen that mutations will not affect treatment; cancer cells can mutate in such a way that target receptors no longer work. ”

"The likelihood of having multiple mutations that could change all target receptors at once is dramatically reduced with an increase in the number of targets used," continued Morad. "Instead of attacking the receptors one at a time, we attack the receptors three at a time — even cancer cannot change three receptors at once."

In addition, many cancer cells activate detoxification mechanisms under stress from drugs. Cells pump out drugs or change them so that they do not function. But Morad said that detoxification takes time. When the toxin is strong, he has a good chance of killing cancer cells before their detoxification occurs, which is what he expects.

Many cytotoxic anticancer drugs are targeted to fast-growing cells. But cancer stem cells do not grow quickly, and they can avoid treatment. Then, when the treatment ends, they can cause cancer again.

“If you don’t kill the entire cancer, the remaining cells may mutate again, and then the cancer will return, but this time it’s drug resistant,” Morad said.

He explained that because cancer cells are caused by mutations that occur in cancer stem cells, most of the over-expressed proteins targeted by anticancer therapies also exist in cancer stem cells. The MuTaTo multipurpose attack ensures that they will also be destroyed.

Finally, some cancers erect shields that cause problems with large molecules, such as antibodies. MuTaTo acts like an octopus or spaghetti and can penetrate places that other large molecules cannot penetrate. Morad said that the MuTaTo peptide parts are very small (12 amino acids long) and do not have a rigid structure.

“This should make the entire molecule non-immunogenic in most cases and allow repeated administration of the drug,” he said.

Morad said that their discovery can also reduce the side effects of most cancer treatments that are associated with drugs that interact with improper or unnecessary targets or right targets, but with normal cells. He said that having a combination of several highly specific peptides on a general basis for each type of cancer in MuTaTo will increase the specificity due to the avidity effect. In addition, in most cases, normal cells that have a common protein with cancer cells do not hyper express it.

“We notice a big difference between the two types of cells and significantly reduce side effects,” said Morad.
He equated the MuTaTo concept with a triple cocktail of drugs that helped transform HIV from a death sentence into a chronic but manageable disease.
Nowadays, HIV patients take protease inhibitors in combination with two other drugs called reverse transcriptase inhibitors. The combination of drugs destroys HIV at different stages of its replication, inhibiting an enzyme that is critical at the early stage of HIV replication, and an enzyme that functions closer to the end of the HIV replication process.

“We used to give several drugs to HIV patients, but we gave them one at a time,” explains Morad. “During the treatment, the virus mutated, and HIV began to attack again. Only when the patients started using the cocktail did they manage to stop the disease. ”

Now, he says, people with HIV are carriers of the infection, but they no longer get sick.

MuTaTo treatment will be personalized. The patient will take a biopsy in the laboratory, analyze it to find out which hyper receptors are expressed. Then the patient will be given a cocktail of molecules that is needed in the treatment of his particular disease.
However, unlike HIV, when patients have to take a cocktail throughout their lives, in the case of MuTaTo, the cells will be killed and the patient can probably stop treatment after a few weeks.
The company is currently engaged in patents on specific peptides, from which they will collect a large bank of toxic peptides, Aridor said.

Now the company has completed its first experiment with mice: the treatment inhibited the growth of human cancer cells and had no effect on the cells of healthy mice. AEBi is on the verge of clinical trials that can be completed in a few years and provide early access to treatment in special cases.

Aridor said: "Our results are repeatable and verifiable."

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