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Toward a Cure for Cancer & Alzheimer’s?

 It’s About How Cells (Fail to) Take Out the Trash

By Shlomo Maital

Prof. Ido Amit

   Prof. Ido Amit is a scientist at Israel’s Weizmann Institute, and heads an immunology lab there.  On his website, he writes:  “You don’t learn to walk by following rules. You learn by trying and falling over.”  

     In this weekend’s Haaretz magazine, science writer Asaf Ronel has a lovely cover article (in Hebrew) about a possible breakthrough by Amit, in treating cancer and even Alzheimer’s.

     I will try to explain it.

     In order for cancer cells to spread through our bodies, they have to evade and defeat our immune system – specifically, immune cells that attack and kill these foreign invaders.  But how exactly do cancer cells defeat our immune system?

       Amit’s lab has perhaps discovered how.  Cancer cells, it is claimed,  latch on to specific cells in the body, whose purpose it is to ‘take out the trash’ made by the body’s cells, as they consume energy and do their jobs.  Cancer cells transform those kidnapped ‘garbage truck’ cells and  turn them into cells that that deprive the body’s cells of energy ..basically, making the ‘garbage trucks’ collect energy from the body’s immune-response cells and not just the trash. 

       Immunotherapy helps the body’s immune-response cells to identify and destroy cancer cells. But cancer cells can neutralize those immune-response cells by using the ‘garbage truck’ cells to deprive them of much-needed energy. Without energy, the immune cells can’t do their job.

       Amit’s lab believes it has a way to neutralize the kidnapped ‘garbage truck’ cells and disable them, so that the body’s tissues get the needed energy – in particular, the immune-response cells.   Once the immune-response cells get the needed energy, they are able to successfully attack and destroy the cancer cells.

        Several Pharma companies are at work on finding drugs that implement Amit’s approach.    There is hope that as a result,  many of the 10 million persons who die worldwide annually of cancer may be saved.  

         But wait.  There is more.

         We know that Alzheimer’s and other forms of dementia afflict 50 million people worldwide.  Alzheimer’s is linked to plaque that forms in the brain and ‘gums up the brain cells’, like putting sugar into someone’s gas tank (don’t try this at home) that gums up the carburetor or fuel injection. 

          Amit believes the cause may be the same ‘garbage truck’ cells in the brain, that somehow become unable to ‘take out the trash’ and get rid of the plaque and waste generated by brain cells (which generally work very hard every minute of the day).  As that trash accumulates in the brain, the brain ceases to function properly – more or less, like the streets of, say, Tel Aviv, when the garbage collectors go on strike and the trash accumulates in piles on streets and sidewalks..

       Amit says if we catch early-stage dementia, and repair the ‘garbage truck’ cells, maybe we can delay or prevent the disease’s onset and keep the brain cells trash-free..

        How soon will there be drugs that implement his finding?  Amit believes – two to four years

         Hang on there, Snoopy.  Help may be on the way. 

         To discover this, Amit had to invent new technologies that enable the study of individual cells.  He was told by experts that what he was attempting was impossible.  As with many breakthroughs,  he persisted. 

         I myself have survived prostate cancer, a close call,  and the only thing I really fear in this world is having my brain gummed up with plaque.  So I will follow Amit’s progress very closely.  A lot is at stake.    

A Look Inside Virus-Infected Cells

By Shlomo Maital

   Researchers at Israel’s Weizmann Institute have provided us with a revealing look inside cells infected with novel coronavirus. The research was led by Prof. Ido Amit, Dept. of Immunology, and reported in a front-page article in today’s Haaretz daily, by Ido Efrati.

       Amit is an expert in single-cell genomics, in which scientists analyze the DNA of single human cells. By analyzing single cells of severely ill patients with COVID-19, moderately ill ones and healthy persons, the scientists can map precisely how the insidious virus wreaks its havoc.

       Here is a short summary. The virus attacks epithelial cells in the lungs; these cells transport oxygen from the lungs to the blood, where it is distributed to the body’s vital organs.   This attack induces macrophages, a specialized cell that detects and (tries to) destroy the virus.   The Weizmann Institute scientists found that in seriously ill patients, the macrophages were replaced by monocytes, which are blood cells created by the body’s immune reaction. Ironically, an excess of those monocytes (as the body fights back against the virus) produces an overload of the immune reaction, known as a cytokine storm. This creates massive inflammation and actually hampers the immune system.

     The researchers, who have cooperated with other scholars in China and Italy, note that this cytokine storm occurs even before other signs appear.

     This suggests that a blood test could reveal which patients are high risk, even before their lungs show distress.   They also note that perhaps drugs or treatments can be developed to protect the lungs’ macrophages before the virus can seriously damage them.

     It is clear that those with unhealthy lungs, perhaps through smoking or other conditions, are more vulnerable.

       It is taking time, but thanks to cooperation among scientists worldwide, a clearer picture is beginning to emerge of precisely how the novel coronavirus makes us ill and kills some of us. This knowledge will ultimately lead to effective treatments.

 

 How to Cure Cancer: Zelig Eshhar’s Breakthrough

By Shlomo Maital

Eshhar

Prof. Zelig Eshhar

 

   Media reports last week brought exciting news about a new breakthrough in the fight to cure cancer.

       In an article in the journal Science Translational Medicine, a team at the University of Pennsylvania’s Abramson Cancer Center and the Perelman School of Medicine reported that 27 out of 29 patients with an advanced blood cancer saw their cancers go into remission or disappear altogether when they received genetically modified T-cells that were equipped with synthetic molecules called chimeric antigen receptors, or CARs. Those T-cells were able to target and destroy the tumor cells – specifically the ones that were responsible for the acute lymphoblastic leukemia the patients were suffering from. According to officials at the Fred Hutchinson Cancer Research Center, where the research was carried out, patients in the trial – some of whom were told in 2013 they had barely a few months to live – not only survived, but now, after the therapy, “have no sign of the disease.”

One of the pioneers of this approach is Prof. Zelig Eshhar, of Israel’s Weizmann Institute. According to press accounts:   “Eshhar has been conducting T-cell research for over a decade, and in 2014 was recognized by leading industry publication Human Gene Therapy for his work, along with Dr. Carl June of the University of Pennsylvania for their work in the field. In an article called “From the Mouse Cage to Human Therapy: A Personal Perspective of the Emergence of T-bodies/Chimeric Antigen Receptor T Cells,” published for the occasion, Eshhar laid out the mechanics of CAR T-cell immunotherapy – showing how his work on mice progressed to the point where the American team was able to pick up the cudgel and conduct a study on humans. With that. Eshhar cautioned Wednesday, the breakthrough did not in any way represent a “cure for cancer” – at least not yet. “Obviously much more work is needed,” he said. “One issue with this kind of therapy is that you have to develop specific T-cells for each kind of cancer. But studies like those are a great impetus to move forward with research. I believe the day will come when we will see many more cancers treated in this manner.”

     T-cells are the white blood cells produced by our immune systems that fight invading germs and microbes (and cancer cells). But they are generally too weak to fight off cancer cells, which have several clever defense mechanisms. However, by removing T-cells, and genetically modifying them, they can be strengthened – a bit like taking a Chevrolet Impala and souping it up with a Corvette 400 hp. engine. Eshhar has cured mice of cancer using this method, and the U. of Pennsylvania team extended his method to humans, with success.

     Will such T-cell therapy defeat all cancer, not just a form of leukemia and lymphoma? Let us hope!    

Blog entries written by Prof. Shlomo Maital

Shlomo Maital

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