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How to Cure Cancer: Zelig Eshhar and the $12 b. Exit

By Shlomo Maital

Prof. Zelig Eschar

  Last year, I blogged about a remarkable breakthrough in research on fighting leukemia and lymphoma.

“Media reports last week [2016] brought exciting news about a new breakthrough in the fight to cure cancer. Cancer patients 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.”

Yesterday brought an interesting postscript, with an Israeli perspective.

    Kite Pharma, a US company founded by an Israeli scientist, Dr. Arie Belldegrun, acquired the patent rights to Eschar’s breakthrough, in a very complicated deal. Now, according to the Wall St. Journal, a biotech company called Gilead (“Balm of Gilead”, from the Bible), with $30 b. in annual revenues, has acquired Kite Pharma, for a staggering $12 billion. And that figure is not overpriced.

   One reason for the high price is that recently Novartis received FDA approval for a similar drug, based on genetically engineering T-cells to recognize and kill cancer cells, this one for leukemia.   Kite and Gilead may soon get FDA approval for their drug aimed at non-Hodgkin’s lymphoma.

   Belldegrun is a remarkable individual.   He is a Professor at UCLA, a specialist in urological oncology. And at the same time he is a serial, successful entrepreneur, having done several exits (and earned many hundreds of millions of dollars), and is founder of Kite. He recognized the potential of Eschar’s breakthrough and managed a complex deal in which Kite acquired the rights to the patent. Belldegrun studied at Israel’s Weizmann Institute and Hebrew University Medical School, and moved to the US early in his career. He collaborated closely with Dr. Steven Rosenberg, of the U.S. National Institutes of Health.

     The new approach to fighting cancer – teaching T-cells how to spot cancer cells, which are cleverly disguised, tear off their disguise and kill them – is highly promising. Kudos to Professor Eschar, Dr. Belldegrun and to those who were early investors in Kite – and profited.



Melanoma: Outsmarting the Devilish Cancer Cell

By Shlomo Maital

Carmit Levy

Dr. Carmit Levy

     Despite countless billions of dollars in research funds, cancer continues to take its toll. The principle therapy continues to be chemotherapy, which by brute force poisons cancer cells and barely leaves other cells mostly unharmed.   Is it time to rethink?

       Tel Aviv University researcher Dr. Carmit Levy, together with an international team of researchers, including those from Germany’s Heidelberg Univ., have come up with breakthrough findings for skin cancer (melanoma) which kills one person every 52 seconds in the world, or some 90,000 people annually. Their findings are to be published in a leading scientific journal. Levy has just returned to Israel after a stay at Harvard.

         The team found that cancer cells begin in the epidermis, the outer layer of the skin, which has no blood vessels. Without blood and the nourishment it brings the cancer cannot spread (metastasize). So – it needs to penetrate the dermis, the skin layer below the epidermis, which does have blood vessels. But the dermis has immune cells that kill the cancer. How can the cancer cell invade enemy territory and survive?

     Simple. It sends out tiny nano-bubbles, with genetic material, that alter cells in the dermis and make them friendly for invasion. (Perhaps, like the Vichy France government that welcomed the Nazis in World War II). The melanoma, with its new blood supply, is now set to spread through the body and in many cases, kill the body itself.

   This discovery may make it possible to neutralize those tiny nano-bubbles, and keep them from preparing a friendly invasion site.   If melanoma can be stopped from metastasizing, the localized cancer can be removed in simple surgery. This is now the goal of the Levy team.

     It continues to amaze me, how evolution has enabled cancer cells to adapt, creating incredible complex mechanisms to defeat the body’s immune system, which itself has evolved and is exceptionally powerful and sophisticated. This is an endless war of escalation, in which cancer so far has had the upper hand. Thanks to Dr. Levy, perhaps we can gain some ground.



 How to Cure Cancer: Zelig Eshhar’s Breakthrough

By Shlomo Maital


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!    

Mayo Clinic Can Make Cancer Cells Normal!

By Shlomo Maital

Panos Anastasiadis

Professor Panos Anastasiadis

An exciting report recounts how Mayo Clinic scientists, in Florida, led by Prof. Panos Anastasiadis, have done the impossible – made cancerous cells healthy again.

  Here is how the London Daily Mail reported the breakthrough:    “Scientists have found a code for turning off cancer, it was announced today.  In exciting experiments, they made cancerous breast and bladder cells benign again. And they believe many other types of cancer should be in their grasp. They said that their work reveals ‘an unexpected new biology that provides the code, the software for turning off cancer’.  Most importantly, it uncovers ‘a new strategy for cancer therapy’.  In landmark research, Mayo Clinic scientists made cancerous cells benign again. And they believe many other types of cancer should be in their grasp.”

   What the scientists did, is inject micro-RNA into the cancerous cells, which turned off the cells’ desperate cancerous need to divide again and again, and spread.  

  According to the Daily Mail:  “The work is still at an early stage but brings with it hope that cancer will take fewer lives in the future. Unlike conventional cancer drugs, which work by killing cancer, the  work aims to disarm it and render them harmless.  The breakthrough focuses on a protein called PLEKHA7 that helps healthy cells clump together.  The research showed it to be missing or faulty in a range of cancers.  When this happens, key genetic instructions to the cells are scrambled and they turn cancerous. A research team, led by Panos Anastasiadis, was able to reset the instructions – turning off the cancer.  Experiments in a dish showed that human cells from highly dangerous bladder cancers can be made normal again.   Dr Anastasiadis said: ‘Initial experiments in some aggressive types of cancer are indeed very promising.’  He thinks the approach, detailed in the journal Nature Cell Biology, would apply to most cancers, other than brain and blood cancers.”

    For years, scientists have sought a new approach to treating cancer, other than the some 200 drugs used for chemotherapy, that are toxic and cause great suffering, and often do not work. 

      Perhaps this is the ‘silver bullet’ breakthrough?



Health Insurers & Pharma Benefits: The New FDA

Will Kite Kill Cancer (Affordably)?

By Shlomo Maital

 Kite pharma

 My university, Technion, is one of the few science universities with a President who is both a world-class scholar and successful entrepreneur. Prof. Peretz Lavie is a pioneer in sleep research, and his 10 patents have helped build two or three successful companies that treat sleep apnea, a common disorder that afflicts millions.  In a guest talk to my Entrepreneurship class at Technion, Prof. Lavie explained that agreement by health insurance companies to pay for drugs or treatments is a more crucial obstacle for companies and inventors than perhaps even the FDA.  Your drug may prove effective in Stage 3 clinical trials and pass the FDA, but – if it’s too expensive, insurers won’t pay for it and it is therefore doomed.  As an entrepreneur, Lavie successfully dealt with this problem.  By carefully collecting sleep apnea data, he was able to show the insurers why treatment was cost-effective. 

    Recently, we saw a great example of why insurers are the “new FDA”.  Gilead Sciences developed Harvoni, a Hepatitis C drug that costs $94,500 a year.  It competes with AbbVie’s $83,319 drug Viekira Pak.  The FDA approved Harvoni.  But America’s largest pharma benefits company (which provides drugs as part of health insurance) removed Harvoni from its approved list, saying it was more expensive than AbbVie’s drug Viekira Pak and not much more effective.  Gilead’s stock plunged; it fought back and slashed its prices. 

     The key role of insurers came to the fore in recent days.  Kite Pharma and its Israeli-born and educated CEO Dr. Arie Belldegrun has developed an experimental cancer treatment, a very expensive one, which costs hundreds of thousands of dollars.  The complex diagram shows how it works.  Briefly,  here is how:

       Cancer cells are removed from the patient’s body, treated – and then put back. The treated cells (unlike untreated cancer cells) trigger a powerful immune response.

        To explain:  Cancer cells cleverly shut down the body’s immunse system response; but Kite’s genetically engineered autologous T cell therapy fights back, tricks the cancer cells and restores  the immune system’s ability to recognize and eradicate tumors.     “In August 2014, Kite Pharma announced findings from its ongoing clinical trial: 12 of 13 evaluable patients with advanced B-cell malignancies had complete remissions (8 patients) or partial remissions (4 patients) resulting in a 92% objective response rate. The results support Kite Pharma’s plan to file an Investigational New Drug (IND) application in the fourth quarter of 2014 to initiate a clinical trial of Kite Pharma’s lead CAR-based product candidate, KTE-C19, in patients with DLBCL.”

     Kite has a powerful strategic partner: Amgen, a huge biotech company.  “In January 2015, Kite Pharma and Amgen entered into a strategic research collaboration and license agreement to develop and commercialize the next generation of novel Chimeric Antigen Receptor (CAR) T cell immunotherapies based on Kite’s engineered autologous cell therapy (eACT™) platform and Amgen’s extensive array of cancer targets.”

     But the hitch is:  will the health insurance companies and pharma benefits companies pay for this hugely expensive though lifesaving therapy?  Kite is aware of the problem and is trying to deal with it.

     Stay tuned. 

Targeted Drug Delivery: Promising New Assault on Cancer

By Shlomo   Maital   


According to today’s Haaretz newspaper,  one of my Technion colleagues,  Dr. Avi Schroeder (see photo),  of the Chemical Engineering faculty,  has developed a promising new innovation for curing cancer.  He heads the Laboratory for Targeted Drug Delivery and Personalized Medicine Technology. 

  “Being an engineer, I thought of an engineering approach to prescreen drugs on a personal basis BEFORE we begin a treatment cycle,” he explains.

   The idea is simple.  It is like testing for an allergy, by scratching the skin and applying a tiny amount of the allergenic material.   In Schroeder’s approach, the cancer patient is given a battery of drugs, in miniscule doses – and then tested to see which if any actually reach the tumor, penetrate the cancer cells (which have clever defences) and kill them.  There are over 200 different anti-cancer drugs.   Each individual may react differently to them, depending on their genetic makeup and the type of cancer they have, and even depending on their gender.  (Thanks to studies done at Univ. of California, Irvine, we now know that women react completely differently to drugs than men – and America’s FDA now requires drug testing to include gender in the clinical trials, both for mice and for humans, to see if there are indeed differential gender effects). 

     In his method, Schroeder creates nanoparticles containing drugs “barcoded” with DNA.  The process of attaching DNA to each molecule of the drug is not expensive any more, because DNA has become quite cheap.  These nanoparticles are injected into the patient’s blood stream.  They travel around the body and when they identify a tumor, the particles penetrate its cells through micro-fissures that cancer cells typically have.  The drugs are then released into the cells.  Some of the drugs will work and kill the tumor; some won’t.  To find out, the tumor is then biopsied, and cells are examined individually.  The dead cells are separated from the living ones to see “which drug barcode is the most associated with killing cancer cells, and which are not.” 

    So far, testing is in the preclinical stage.  Schroeder is looking for financing to bring the idea to market.   The beauty is,  it is based on drugs that already exist.

Larry Page: As Innovator Role Model

By Shlomo   Maital    

Larry Page

Fortune magazine has chosen Larry Page (Dec. 1 issue) as Business Person of the Year. The feature article begins with a revealing joke, told often around Google. At Google’s “moon shot” Google X center, where self-driven cars, high-altitude wind turbines, and stratospheric balloons for Internet access are developed, a ‘brainiac’ creates a time machine. As the scientist reaches for the power cord to start a demo for Larry Page, Page says: “Hey! Why do you need to plug it in!?”

   For a decade Page was one member of a triangle – Sergei Brin, Eric Schmidt, and Page – that led Google. In 2011 Page took over as CEO.   Turns out he is a good manager. In the past three years, Google has grown 20% annually, and has quarterly revenue of $16 b. It has $62 billion in cash. Page invests heavily both in Google’s core business (he says he argued with Steve Jobs, who said, ‘you guys are doing too much’) and in far-flung new projects.   According to Fortune, in the past year, Google has invested in artificial intelligence, robotics and delivery drones. It has expanded its venture unit, which invests in startups and is a kind of scouting team. It bought Nest, a smart-home startup. It invested in Calico, a biotech firm.  

   Originally Google set out to “organize the world’s information and make it universally useful and accessible”. Today that vision is too narrow. Page says he wants Google to change the world in ways most of us cannot imagine.

   Some say Google is too narrowly focused on advertising revenue. But YouTube now brings in $6 billion in annual revenues. Page continues to invest in bold ventures, to ensure the company’s future. He is making ‘credible bets’ on the home, the car, and wearable devices.

   Most amazingly, Google has a secret facility where a team of scientists are working on a project that will chemically ‘paint’ tiny nanoparticles, with a protein, so they bind to things like cancer cells.   And then concentrate them through magnetized wearable devices, so they can be ‘queried’. This would enable constant monitoring and detection of a whole host of devices.   Outside Google’s core competence?   Not at all.

   Page regards some of his bold bets as a portfolio bucket. Some will pay off. Many won’t. He doesn’t think the risk is high. By the time you want to put large sums of money into something, you pretty much know whether it will be profitable, he says. For him, not taking risks is the biggest risk of all.

How to Build Great Ideas On Key Facts

By Shlomo   Maital


 How do you develop great ideas for startups (whether social or business-oriented), that truly meet unsatisfied wants and change the world?

   I got an idea about ideas, from the current issue of TIME Magazine, of all places (Sept. 8 and 15 double issue).    This issue has an incredible number of interesting facts, presented creatively, visually. 

   You get great ideas from one key fact.  That fact at one fell swoop demonstrates vividly the need, and sets the stage for thinking big,  for tackling huge problems with huge impact, if successful.


  •    At present,  2.4 billion people are connected to the Internet; 44.8 percent of them are in Asia.  That means that 4.6 billion people have NO Internet connection.  How can this pressing need best be met?   Challenge:  Find a way to bring the Internet to 4.5 billion people who currently lack it. 
  •    At present, 2.8 billion people in the world cook over open fires; 4.3 million people die each year due to indoor air pollution, caused by open fires used for cooking. Most of the deaths are women and children. Challenge?  Find a way to save millions of lives, lost through inhalation of smoke from indoor cooking fires; 
  • Half the world’s children go to schools without electricity. Challenge: Find a way to bring electricity to the 1.3 billion people in the world who have no access to it.
  • Between 1998 and 2010,    463 children have died of overheating or hyperthermia in cars in the United States, the majority of whom were accidently left behind by caregivers.   Challenge: Find a simple way to prevent this.
  •    60 million plastic water bottles are used annually in the United States alone. Challenge:  Find a biodegradable plastic, that degrades in 90 days, and that also fertilizes plants.  (One of my students in Shantou Univ. China, is close to a solution).

*  Apple has $158.8 billion in unspent cash reserves.  Huge cash reserves are held (abroad) by Microsoft, Cisco, Google, Pfizer, and other U.S. companies.  Challenge: Feasible legislation to get them to bring the money home and invest it in America.

   And, one example of how this could work.

  • Why don’t we get heart cancer???   Because tumors grow when cells divide and multiply uncontrolled – but heart cells never split and multiply, beginning shortly after birth, unlike other cells.  


  •    Idea: Technion Prof. Yoram Palti thought that if you put an electro-magnetic field around, say, the brain, when brain tumor cells tried to divide, creating a narrow cell wall, you could explode them with the magnetic field. This could treat ‘untreatable’ tumors and stop them in their tracks. Basis: Cell division is largely by sick ‘cancer’ cells.   Palti, who is over 70, and his startup now have a proven device that stops brain tumors in their tracks, as well as lung cancer (very hard to treat).  Check out “Novocure”. Thanks, Prof. Palti!

Breakthrough:  Vaccine Against Cancer!

by Shlomo Maital

cancer vaccine

   Cancer immunology [use of the body’s own immune system to kill cancer cells] has been chosen as the “Breakthrough of the Year” by the editors of Science. A fascinating report was published in the December 20 issue. (This blog is longer than usual, because the topic is so important).

   For example: According to the U.S. National Institutes of Health: The photo shows an aspirin-sized disk, the first therapeutic cancer vaccine implanted beneath the skin. “We know it can eradicate melanoma in mice—the deadliest form of skin cancer—with impressive efficacy . Now, it’s being tested in human trials.”

One day, hopefully, chemotherapy may be replaced by immunotherapy. Instead of poisoning cancer (and our own body), we may be able to trick cancer cells, which are good at defeating the body’s own T-cell immune system, and enable our T-cells to kill cancer cells before they become tumors or even after.

What is the science here? According to the NIH, vaccines prevent illnesses, like smallpox, by introducing dead or weakened germs, to teach the body to create antibodies if it does appear. We already have vaccination against the human papilloma virus (HPV)—a powerful way to prevent cervical cancer. The new anti-cancer vaccines work differently. They’re given to patients who have already been diagnosed with cancer. Once given they “behave like traditional vaccines—by teaching the immune system how to seek out and destroy a target—in this case, a tumor. “

“ A couple of cancer vaccines have already been approved by the FDA. However, producing these vaccines is typically a cumbersome, time-consuming, and expensive process. First, immune cells are taken from a patient. The cells are modified and reprogramed in the lab, and then they are injected back into the patient. In the vaccines approved to date, this elaborate production line has extended patient life—but only slightly. And so, some researchers began to look for a simpler, and perhaps more effective, way to make therapeutic cancer vaccines. About four years ago, an NIH-funded, multidisciplinary team based in Boston and Cambridge came up with an approach that would modify and reprogram patients’ immune cells—inside the body, not in a lab!! The team first developed a porous polymer implant, made from the same material as biodegradable sutures and meshes. Then they infused the disk with a collection of three immune stimulants that recruit the immune cells, activate them, and imprint them with a chemical signature of the tumor that is targeted for destruction.

“The first of the three immune stimulants is a drug called leukine (also known as GM-CSF), which summons millions of dendritic cells, key immune cells, to enter the implant. The second is DNA that mimics viral and bacterial DNA and sends a danger signal that activates these cells. The third ingredient is the personalized part of the recipe: a combination of proteins made from the patients’ own tumor. It gives the dendritic cells the unique signature of that person’s tumor, which they share with the warrior T-cells. The “educated” T-cells are then primed to hunt and obliterate the tumor.”

The new approach is metaphorically like training cancer-killer cells to a) spot cancer, and b) kill it, by first teaching them to recognize the enemy and then, giving them ‘martial arts’ skills to destroy it.

Some of the most advanced work in the world on cancer immunology is done in my country, Israel. Prof. Leah Eisenbach, at the Weizmann Institute, Rehovot, has done breakthrough work. A company known as Compugen has developed antigens proven useful against cancer, and sold two of them for hundreds of millions of dollars to Bayer.

We know today that there are more than 120 different types of cancer. Each requires its own variant of chemotherapy. While survival rates have risen enormously, there has to be a better way than ‘tailored poison’. There is. Immunotherapy may point the way. If you know someone who has cancer, or whose loved ones have it, draw their attention to this new breakthrough. There is definitely hope, and the progress may be relatively rapid.



Blog entries written by Prof. Shlomo Maital

Shlomo Maital
June 2019
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