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Friday, 28 February 2020

Israeli Scientists Claim To A Cure For Cancer

Israeli Scientists Claim They're On The Path To A Cure For Cancer

It doesn't seem possible. But they say it's true. A small team of Israeli scientists is telling the world they will have the first “complete cure” for cancer within a year, The Jerusalem Post reported on Monday. And not only that, but they claim it will be brief, cheap and effective and will have no or minimal side-effects.



Illustration of a breast tumour.
 GETTY
“We believe we will offer in a year’s time a complete cure for cancer,” said Dan Aridor, chairman of the board of Accelerated Evolution Biotechnologies Ltd. (AEBi), a company founded in 2000 in the ITEK incubator in the Kiryat Weizmann Science Park in Ness Ziona, Israel, just north of the Weizmann Institute of Science in Rehovot, Israel. 
A development-stage biopharmaceutical company engaged in discovery and development of therapeutic peptides, AEBi developed the SoAP platform, a combinatorial biology screening platform technology, which provides functional leads—agonist, antagonist, inhibitor, etc.—to very difficult targets.
Still skepticism was high among those in the know. Weighing in on behalf of the American Cancer Society (ACS) on his blog, “A Cure For Cancer? Not So Fast,” Len Lichtenfeld, MD, ACS chief medical officer cautioned: “…it goes without saying, we all share the aspirational hope that they are correct. Unfortunately, we must be aware that this is far from proven as an effective treatment for people with cancer, let alone a cure."
Lichtenfeld went on to list several key points that he says must be kept in mind no matter what media reports say:
  • This is a news report based on limited information provided by researchers and a company working on this technology. It apparently has not been published in the scientific literature where it would be subject to review, support and/or criticism from knowledgeable peers.
  • My colleagues here at American Cancer Society tell me phage or peptide display techniques, while very powerful research tools for selecting high affinity binders, have had a difficult road as potential drugs. If this group is just beginning clinical trials, they may well have some difficult experiments ahead.
  • This is based on a mouse experiment which is described as “exploratory.” It appears at this point there is not a well-established program of experiments which could better define how this works—and may not work—as it moves from the laboratory bench to the clinic.
  • We all have hope that a cure for cancer can be found and found quickly. It is certainly possible this approach may be work. However, as experience has taught us so many times, the gap from a successful mouse experiment to effective, beneficial application of exciting laboratory concepts to helping cancer patients at the bedside is in fact a long and treacherous journey, filled with unforeseen and unanticipated obstacles.
  • It will likely take some time to prove the benefit of this new approach to the treatment of cancer. And unfortunately–based on other similar claims of breakthrough technologies for the treatment of cancer–the odds are that it won’t be successful.
“Our hopes are always on the side of new breakthroughs in the diagnosis and treatment of cancer. We are living in an era where many exciting advances are impacting the care of patients with cancer,” Lichtenfeld went on. “We hope that this approach also bears fruit and is successful. At the same time, we must always offer a note of caution that the process to get this treatment from mouse to man is not always a simple and uncomplicated journey.”
Called MuTaTo (multi-target toxin), researchers said the drug is essentially "on the scale of a cancer antibiotic–a disruption technology of the highest order."
Aridor told The Jerusalem Post: “Our cancer cure will be effective from day one, will last a duration of a few weeks and will have no or minimal side-effects at a much lower cost than most other treatments on the market. Our solution will be both generic and personal.”
Currently in development by AEBi under the leadership of CEO Dr. Ilan Morad, the potential game-changer in the world-wide fight against cancer will use a combination of cancer-targeting peptides and a toxin that will specifically kill cancer cells.
The Jerusalem Post reported that the anti-cancer drug is based on AEBi's so-called SoAP technology, which belongs to the phage display group of technologies. With it, “scientists introduce DNA coding for a protein, such as an antibody, into a bacteriophage – a virus that infects bacteria. The protein is then displayed on the surface of the phage. Researchers can use these protein-displaying phages to screen for interactions with other proteins, DNA sequences and small molecules.”
A team of scientists won the Nobel Prize last year for their work on phage display in the directed evolution of new proteins – in particular, for the production of antibody therapeutics, The Jerusalem Post reported. “AEBi is doing something similar but with peptides, compounds of two or more amino acids linked in a chain.” According to Morad, peptides have several advantages over antibodies, including that they are smaller, cheaper, and easier to produce and regulate.
According to an article in Elsevier’s Science Direct, peptide therapeutics have played a notable role in medicine since the advent of insulin therapy in the 1920s. “Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace,” the article states.
The International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) estimates the  global cancer burden to have risen to 18.1 million new cases and 9.6 million deaths in 2018. The IARC reports 1 in 5 men and 1 in 6 women worldwide develop cancer during their lifetime, and 1 in 8 men and 1 in 11 women die from the disease. In addition, every sixth death in the world is due to cancer, making it the second leading cause of death, second only to cardiovascular disease.
Morad said in its infancy, AEBi was essentially “doing what everyone else was doing, trying to discover individual novel peptides for specific cancers.”
But then Morad and his colleague, Dr. Hanan Itzhaki, began attempting to identify why other cancer-killing drugs and treatments didn’t work or eventually failed. And they say they’ve found a way to counter that effect.
Morad said most anti-cancer drugs attack a specific target on or in the cancer cell. “Inhibiting the target usually affects a physiological pathway that promotes cancer. Mutations in the targets – or downstream in their physiological pathways – could make the targets not relevant to the cancer nature of the cell, and hence the drug attacking it is rendered ineffective,” he told The Jerusalem Post.
“In contrast, MuTaTo is using a combination of several cancer-targeting peptides for each cancer cell at the same time, combined with a strong peptide toxin that would kill cancer cells specifically,” Morad said. “By using at least three targeting peptides on the same structure with a strong toxin, we made sure that the treatment will not be affected by mutations; cancer cells can mutate in such a way that targeted receptors are dropped by the cancer.”
“The probability of having multiple mutations that would modify all targeted receptors simultaneously decreases dramatically with the number of targets used,” Morad continued. “Instead of attacking receptors one at a time, we attack receptors three at a time – not even cancer can mutate three receptors at the same time.”
According to Morad, many cancer cells activate detoxification mechanisms when in stress from drugs and the cells pump out the drugs or modify them to be non-functional. Morad told The Jerusalem Post that detoxification takes time, and he’s banking on a strong toxin that will have a high probability of killing the cancer cell before that detoxification occurs.
“Many cytotoxic anticancer treatments aim at fast-growing cells. But cancer stem cells are not fast growing, and they can escape these treatments. Then, when the treatment is over, they can generate cancer again,” The Jerusalem Post reported.
“If it does not completely annihilate the cancer, the remaining cells can start to get mutations again, and then the cancer comes back, but this time it is drug resistant,” Morad said.
Because cancer cells are born out of mutations that occur in cancer stem cells, most of the over-expressed proteins which are targeted on the cancer cell exist in the cancer stem cells. “MuTaTo’s multiple-target attack ensures that they will be destroyed as well,” he said.
Finally, some cancer tumors can erect shields which prohibit large molecules from accessing them. “MuTaTo acts like an octopus or a piece of spaghetti and can sneak into places where other large molecules cannot reach,” Morad said. “The peptide parts of MuTaTo are very small (12 amino acids long) and lack a rigid structure. This should make the whole molecule non-immunogenic in most cases and would enable repeated administration of the drug.”
Morad said AEBi's discovery could also decrease the sickening side-effects of most cancer treatments dramatically, which are the result of drug treatments interacting with the wrong or additional targets, or the correct targets but on non-cancerous cells. “He said MuTaTo’s having a combination of several highly specific cancer-targeting peptides on one scaffold for each type of cancer cell would increase the specificity to the cancer cell due to the avidity effect. In addition, in most cases, the non-cancer cells that have a protein in common with the cancer cells do not over-express it.”
Morad equated the concept of MuTaTo to the triple drug cocktail that has helped change AIDS “from being an automatic death sentence to a chronic – but often manageable – disease.” Today people with AIDS and HIV are carriers of the disease, but they are not sick anymore. And the reason is the combination of drugs they are given.
“Today, AIDS patients take protease inhibitors in combination with two other drugs called reverse transcriptase inhibitors,” The Jerusalem Post reported. “The drug combination disrupts HIV at different stages in its replication, restrains an enzyme crucial to an early stage of HIV duplication and holds back another enzyme that functions near the end of the HIV replication process.”
“We used to give AIDS patients several drugs, but we would administer them one at a time,” Morad explained. “During the course of treatment, the virus mutated, and the AIDS started attacking again. Only when patients started using a cocktail, were they able to stop the disease.”
According to Morad, the MuTaTo cancer treatment will eventually be designed specifically for each person. A piece of each patient’s biopsy will be given to the lab, which will then analyze it to know which receptors are over-expressed, he said. “The individual would then be administered exactly the molecule cocktail needed to cure his disease.”
But unlike with HIV and AIDS, where patients must take the cocktail for the rest their lives, with MuTaTo, the cells would be killed, and the patient could likely stop treatment after only a few weeks.
Aridor said AEBi is in the process of writing patents on specific peptides, which will be a large bank of targeting toxin peptides wholly owned and hard to break.
The company has finished exploratory mice experiments, which “inhibited human cancer cell growth and had no effect at all on healthy mice cells, in addition to several in-vitro trials,” The Jerusalem Post reported.
Next, AEBi will begin a round of clinical trials which could be completed within a few years and would make the treatment available in specific cases.
“Our results are consistent and repeatable,” Aridor said.
For more on scientists' response to AEBi's announcement, click here.