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Dr. Michael Har-Noy Describes the Development of AlloStimTM – A New Cancer Drug

Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., a biotech company in Israel, has developed a unique biologic, AlloStimTM, which stimulates a patient’s immune response to attack tumor cells.  This enables a patient’s own immune system to scavenge and destroy all metastatic cells.

AlloStimTM is made from T-StimTM cells, which are created using unique, patented methods.

Dr. Michael Har-Noy says that T-StimTM cells are produced outside the body in a bioreactor. T-StimTM cells are produced from T-cell precursors isolated from the blood of normal donors.  Typically, 100 million of these cells can be made from one normal donor’s blood. After a nine day culture process, approximately 10 billion T-StimTM cells can be manufactured.  There is no need to match donor to recipient, as AlloStimTM is intentionally mismatched to the patient receiving it.

To manufacture T-StimTM cells, Dr. Michael Har-Noy says that naïve CD4 cells are cultured on a medium coated with anti-CD3 and anti-CD28 monoclonal antibodies.  These antibodies, as well as cell-to-cell contact, cause activation and maturation of the CD4 cells.  The cells multiply at least 100-fold during the culture process, enabling one donor to produce enough T-StimTM cells for 100 patients.

Dr. Michael Har-Noy indicates that in this environment, the T-StimTM cells mature into memory CD4 cells that produce very high amounts of IL-2, IFN-g and TNF-a when activated.  Additionally, T-StimTM cells express high amounts of CD40L and FasL (a transmembrane protein) on the cell surface.  CD40L interacts with the patient’s innate CD40 immune cells and stimulates these cells to produce Th1 cytokines that kill malignant cells. The FasL enables the patient’s immune cells to kill tumor.

Dr. Michael Har-Noy adds that in order to produce the Mirror EffectTM, the name Immunovative Therapies, Ltd. has given to this novel method of immune manipulation, the T-StimTM cells need activation prior to infusion into the patient.  T-StimTM cells are activated with monoclonal antibody-coated beads that are then filtered out before infusion.  “AlloStimTM” is the name given to the formulated and activated T-StimTM cells.

Dr. Michael Har-Noy says that he is preparing to test AlloStimTM in a Phase II/III double-blind randomized trial of pre-treated metastatic breast cancer patients.

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Dr. Michael Har-Noy Discusses CryoStimTM, a Proprietary Biologic Cancer Treatment

Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd., a biotech company in Israel, discusses CryoStim™, a novel treatment for patients with disseminated metastatic cancer. CryoStim™ combines Immunovative Therapies’ proprietary drug AlloStim™ with cryosurgical ablation of a single tumor lesion (either the primary tumor or a metastatic nodule), thus stimulating a tumor-specific immune response which kills cancer cells wherever they are located in the patient’s tissue.

Dr. Michael Har-Noy goes on to explain that patients are first infused with a dose of AlloStim™, which is a biologic compound designed to elicit rejection by the patient and, in the process, disable the tumor’s immune avoidance mechanism.  The rejection of the AlloStim™ cells results in the patient being immune to the drug. The cancer patient then undergoes a cryoablation procedure designed to freeze a piece of accessible tumor.  This piece of tumor then dies by the process of necrosis, a mechanism that results in an immune response to clean-up and dispose of the damaged and dead cells.  Additional AlloStim™ is injected into the necrotic tumor, resulting in another powerful memory recall immune response to reject this repeated dose of AlloStimTM cells.  The combination of these two powerful immune responses educates the patient’s immune system to recognize the dead tumor cells as dangerous.

Dr. Michael Har-Noy says that years of immunotherapy trials have shown that the immune system of the cancer patient does not recognize the threat of human cancer cells as well as the rodent immune system does in research models of similar diseases.  Dr. Michael Har-Noy goes on to explain that this is why immunotherapy models that work well in rodents fail repeatedly in human trials.

Cancer cells can be destroyed by necrosis through various techniques, such as radiofrequency ablation, cryosurgery, high intensity ultrasound, laser interstitial therapy, and microwave thermotherapy.  Dr. Michael Har-Noy points out that only the cryoablation technique leaves tumor proteins, such as heat shock proteins and tumor antigens, intact.  The methods other than cryoablation cause protein denaturalization through destruction and fusing of the cellular membranes.  Cryoablation is accepted therapy for liver, kidney, lung, prostate, bone, and breast cancers.  Dr. Michael Har-Noy explains that cryoablation causes necrotic cell because of cellular damage by ice crystals, resulting in endothelial and vascular injury and ischemia.

Dr. Michael Har-Noy concludes that the presentation of tumor antigens in an inflammatory environment can disable cancer cells’ ability to avoid the human immune response.  Preliminary test results indicate that CryoStimTM is effective against a wide variety of cancer cell types.

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Dr. Michael Har-Noy Says We Are Losing The Battle Against Cancer

“We are losing the battle against cancer” says Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, a biotech company started in Israel in 2004.  Dr. Michael Har-Noy goes on to say that in past few decades, the incidence of cancer has grown to epidemic proportions, affecting almost one out of every two males and one out of every three females. This means that the current incidence of cancer is 50% greater in men and 25% greater in women than in the previous generation.  The National Cancer Institute predicts that, because of our aging population, the number of cancer cases will almost double by the year 2050.

Dr. Michael Har-Noy indicates that despite decades of research and clinical trials, improvement in overall mortality from cancer has been minimal, and observed reductions in death are primarily due to a decrease in lung cancer deaths secondary to reduced smoking in males, and not from actual advances in cancer therapy.  Furthermore, the overall five-year survival rate for all cancers is virtually the same as it was in 1970; about 50% for all cases combined.

Conventional treatment of cancer has devastating emotional and physical effects and many patients feel that the treatment is worse than the disease.  The financial burden placed on society for treating cancer is also astronomical.  The estimated direct annual cost of cancer treatment has more than quadrupled over the past 20 years.  It has grown from $18 billion in 1985 to $41 billion in 1995 to a staggering $80 billion in 2005. Also, indirect costs from loss of wages, taxes, and overall productivity secondary to cancer were estimated at $100 billion in 1999.

At Immunovative Therapies, Ltd., Dr. Michael Har-Noy is developing unique biologic compounds that stimulate one’s own immune system to kill cancer cells.  Preliminary results of a Phase I/II trial show remarkable efficacy of these compounds across a wide range of cancers.  Definitive randomized Phase II/III trials of these drugs are pending.  

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Dr. Michael Har-Noy Fights Cancer Using Unique Technology

“Cancer is a profoundly debilitating disease that affects millions of people worldwide” says Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd.   Approximately 40% of all people will get cancer in their lifetime.  There are well over one million new cases of cancer diagnosed per year.  The devastating effects of cancer insinuate themselves into all aspects of a patient’s life, as well as those of their families.  Cancer is so difficult to treat because it commonly causes no symptoms until late in its course, and when it is diagnosed it has usually spread beyond the point where it can be eradicated by conventional therapy.  The combination of surgery, chemotherapy, and radiation cannot eliminate every cancer cell.

Immunovative Therapies is a biotech company founded in 2004 in Israel.  The company was first born from the Misgav Venture Accelerator in Israel and received a $300,000 startup grant from the Office of the Chief Scientist.  Dr. Michael Har-Noy and his staff at Immunovative Therapies are developing groundbreaking immunologic compounds that may change the way cancer is treated.

Dr. Michael Har-Noy says that most immune therapies fail for two reasons. First, they attempt to stimulate the wrong immune response – the body’s natural response that has already tried and failed to eradicate the tumor.  Secondly, they fail because they can’t overcome the cancer’s innate ability to elude the immune response that is created.

Dr. Michael Har-Noy has pioneered a completely unique and different immunologic approach to cancer treatment, a process they call the “Mirror EffectTM”, which harnesses the beneficial antitumor response of a successful bone marrow transplant without the devastating side effect of graft-versus-host disease.  Immunovative Therapies’ early testing of their prototype immune compounds has shown promising results across a wide variety of cancers.  Dr. Michael Har-Noy states that AlloStimTM’s anti-tumor activity against pre-treated metastatic breast cancer will soon be evaluated in a large phase II/III randomized trial.

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Dr. Michael Har-Noy Details The Utility Of CRCL Vaccine In Ovarian Cancer

Dr. Michael Har-Noy, CEO of Immunovative Therapies, Ltd., indicates that chaperone-rich cell lysate (CRCL), which is composed of heat shock proteins,  has successfully stimulated the production of tumor-specific immunity against many murine tumors.  Dr. Michael Har-Noy says that scientists have outlined ovarian tumor-derived CRCL’s capacity to turn on dendritic cells to facilitate tumor-specific T-cell production.

CRCL was synthesized from SKOV3-A2 ovarian cancer cells. Dr. Michael Har-Noy says that dendritic cells laden with ovarian tumor-derived CRCL were used weekly to stimulate mononucleocytes from both HLA-A2+  donors and HLA-A2+ ovarian tumor patients.  Cytotoxicity and cytokine production were then measured after four to six treatments.  

Dr. Michael Har-Noy said that CRCL increased both the immune-stimulatory ability of the dendritic cells as well as the amount of interleukin (IL)-12 produced.  T-cells from normal controls as well as from ovarian cancer subjects secreted greater amounts of  interferon-g after re-stimulation with CRCL when compared with dendritic cell stimulation.

Dr. Michael Har-Noy noted that without CRCL stimulation, investigators were able to create cytotoxic T-lymphocyte activity against cancer specific antigens in all healthy donors but in only 25% of patients with ovarian tumors.  Dr. Michael Har-Noy said that this supports the hypothesis that CRCL can effectively treat ovarian cancer and that this individualized vaccine may be an effective new approach to the treatment of this type of cancer.

Dr. Michael Har-Noy is now conducting a Phase I/II study of the CRCL vaccine in different solid tumors.  The study is being run in Bangkok, Thailand, and is being conducted along side a Compassionate Use program.

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Dr. Michael Har-Noy’s CRCL Vaccine Causes Greater Longevity In Advanced Canine Tumor

Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd. describes how a 12-year-old Great Dane with bronchoalveolar cancer, with a life expectancy of less than 1 month, survived over 50 weeks after treatment with Immunovative Therapies, Ltd.’s chaperone-rich-cell-lysate (CRCL).

Before treatment by Dr. Michael Har-Noy, the Great Dane had symptoms consisting of nystagmus and syncope.  Chest X-rays demonstrated a right lung mass.  Ultrasound-guided biopsy demonstrated bronchoalveolar adenocarcinoma, and the dog underwent thoracotomy with lobectomy.  Pathologic analysis of the specimen revealed grade III bronchoalveolar adenocarcinoma with lymph node metastases and blood vessel infiltration.  The average survival for this condition is one month or less.

Using Dr. Michael Har-Noy’s unique synthesizing process, a piece of the tumor was made into a CRCL vaccine, which was given weekly to the afflicted Great Dane.  Imiquimod - a Toll-like receptor 7 agonist - was also administered to the dog for twelve treatments to stimulate the Langerhans cells.  also, the animal was given a single bacillus Calmette-Guerin injection at 30 weeks of treatment to further stimulate its immune system.

The animal remained good health until the tumor recurred during the 44th week after treatment with Dr. Michael Har-Noy’s CRCL drug.  The dog then suffered gastrointestinal bleeding and had to be euthanized at just over 50 weeks after the primary diagnosis was made.

Dr. Michael Har-Noy notes that this is the first report of improved outcome following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a canine. This implies that Dr. Michael Har-Noy’s CRCL vaccine, when administered with Imiquimod, is a safe and effective treatment for canine cancer.

Dr. Michael Har-Noy started Immunovative Therapies Ltd. in Israel in 2004.  Immunovative Therapies, Ltd. makes unique compounds that manipulate a patient’s immune system and help it seek out and kill tumors.

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Dr. Michael Har-Noy Of Immunovative Therapies, Ltd. Discusses Provenge

Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., says that the adverse environment for the development of immunotherapy cancer treatments began to change on April 29, 2010.  On this date, the FDA approved Dendreon’s (DNDN) Provenge® [sipuleucel-T] for the treatment of metastatic castrate-resistant prostate cancer [CRPC] after a randomized clinical trial demonstrated a 4.1 month survival advantage compared to placebo.  Dr. Michael Har-Noy notes that this event reignited enthusiasm for therapeutic cancer vaccines and the stock shares of Dendreon, which traded below five dollars in March 2009, subsequently reached an all-time high of greater than $57 and the company attained a market capitalization of approximately $7.8 billion.  This accomplishment, noted Dr. Michael Har-Noy, demonstrated to the capital markets that FDA would approve a living cell immunotherapy on the basis of a randomized trial showing statistically significant efficacy, even if the efficacy was marginal.  Additionally, Dendreon proved that Medicare would support novel and expensive therapies by approving $93,000 of reimbursement for Provenge®.

However, Dr. Michael Har-Noy went on to say that the commercialization of Provenge® proved to be far more difficult than expected. On August 3, 2011, Dendreon significantly lowered its revenue guidance for 2011 and projected only modest growth.  Dendreon’s revised estimates not only caused a dramatic decline its stock price, but also put a damper on other companies working to commercialize their own cancer vaccines.  Finally, said Dr. Michael Har-Noy, Dendreon filed for Chapter 11 bankruptcy protection on November 10, 2014. The failure of Dendreons’s cancer vaccine again raised fear in the capital market.  Dr. Michael Har-Noy notes that Dendreon’s failure was due to Provenge®’s inscalablilty rather than its marginal efficacy.  Provenge® cannot be mass produced; it has to be painstakingly made from each patient’s individual tumor.

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Dr. Michael Har-Noy of Immunovative Therapies, Ltd. Discusses Cancer Vaccines

Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., says that a major area of research by oncology companies is development of anticancer vaccines. Unlike the prophylactic vaccines that  prevent such diseases as influenza, measles, mumps, polio, smallpox, and pertussis that are familiar to most people, Dr. Michael Har-Noy notes that cancer vaccines are therapeutic vaccines that are given to patients who already have malignancies. They are designed to cause an antitumor immune response. 

The cancer vaccine field has been characterized by a long series of failures, beginning in the 1990s and continuing to the present.  Dr. Michael Har-Noy notes that failures in early cancer vaccine research appear to be secondary to an over-reliance on surrogate endpoints, as opposed to real clinical responses. This is added to the fact that most researchers, says Dr. Michael Har-Noy, don’t understand the role of dendritic cells in immunization.

 However, despite researchers’ improving understanding of dendritic cell biology, and despite improved vaccine design, Dr. Michael Har-Noy says that clinical cancer vaccine studies have continued to fail, even to the present day.  Scientists hypothesize that a major factor in the continuing failures in cancer vaccine research is unstoppable immune suppression in the tumor environment.

Dr. Michael Har-Noy notes that because checkpoint inhibitors appear to work in part by overcoming immunosuppression in the tumor environment, this suggests that giving the vaccines combined with immune checkpoint inhibitors may overcome this source of vaccine failure.  Dr. Michael Har-Noy says that currently, there is only one approved anticancer vaccine, sipuleucel-T, or Provenge. It is approved in the United States and in Europe to treat metastatic castration-resistant prostate cancer.  

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Dr. Michael Har-Noy Is Patenting Technology Of Tremendous Value

Traditional cancer treatments such as surgery, radiation, and chemotherapy don’t have the capability to eliminate metastatic cancer cells throughout a patient’s body.  However, Dr. Michael Har-Noy, founder of Immunovative Therapies, Ltd., an Israeli biotechnology company, notes that the human immune system might be able to do this if properly manipulated.  Dr. Michael Har-Noy indicates that if one could direct a patient’s immune cells to seek out and kill metastases, a complete cure may result.

At Immunovative Therapies, Ltd., Dr. Michael Har-Noy has designed a proprietary treatment he calls the “Mirror EffectTM.  The Mirror EffectTM is a break-through in that it enables us to directly target tumors using the human immune response.  It also interferes with the ability of malignant cells to avoid this response.  The Mirror EffectTM and the creation of drugs that use it may spawn a new industry of medical treatment.  Dr. Michael Har-Noy goes on to say that by properly patenting this technology, Immunovative Therapies, Ltd. could synthesize tremendously profitable compounds.

Dr. Michael Har-Noy and his scientists at Immunovative Therapies, Ltd. are working with patent attorneys to create a portfolio that reflects the huge scope and depth of the Mirror EffectTM and that properly defines its use to enable the immune system to effectively treat some of medicine’s most tenacious diseases.  Dr. Michael Har-Noy notes that the portfolio Immunovative Therapies, Ltd. is building will protect the company’s products and manufacturing techniques but will likely create a new medical field based on immune manipulation and control.

Eventually, Immunovative Therapies, Ltd.’s patent portfolio will a introduce a new oncology division and dramatically alter modern cancer treatment.  Dr. Michael Har-Noy believes that the “Mirror EffectTM” will therefore create limitless value.

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Dr. Michael Har-Noy’s CryoStimTM - a New Biologic Cancer Treatment

Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd., an Israeli biotechnology says that CryoStim™ is a new therapeutic modality for metastatic cancer patients. CryoStim™ involves using Immunovative Therapies, Ltd.’s  proprietary drug AlloStim™ with cryosurgical ablation of an isolated tumor mass  (either metastatic or primary), thereby precipitating a tumor-specific immune cascade which then kills cancer cells anywhere in the patient’s body.

Dr. Michael Har-Noy explains that patients are first given an injection of Immunovative Therapies, Ltd.’s AlloStim™ - a biologic compound designed to cause rejection by the patient as well as neutralization of the cancer’s immune avoidance capabilities.  The rejection of the AlloStim™ cells gives the patient immunity to the compound. The cancer patient then has a cryoablation procedure that freezes a piece of the cancer.  This lesion then breaks down and stimulates an immediate immune response to dispose of the dead and damaged cells.  Dr. Michael Har-Noy says that additional AlloStim™ is then injected into the necrotic mass, causing a powerful memory immune reaction to reject the dose.  These two strong immune responses train the patient’s immune system to see the dead tumor as a threat. 

Many immunotherapy studies have shown that a cancer patient’s immune system doesn’t recognize malignant cells as well as does a rodent’s immune system.  Dr. Michael Har-Noy says, therefore, that successful rodent immunotherapy drugs usually fail when tested in humans.

Malignant cells can be killed using various techniques, such as cryosurgery, radiofrequency ablation, high intensity ultrasound, microwave thermotherapy, and laser interstitial therapy. Dr. Michael Har-Noy notes that only cryoablation leaves tumor proteins, such as tumor antigens and heat shock proteins, intact.  The other methods denature the proteins through destruction and cellular membrane fusion.  Cryoablation is used as adjuvant therapy for liver, lung, kidney, bone, breast, and prostate cancers.  Dr. Michael Har-Noy explains that cryoablation produces cell necrosis using ice crystal damage, which results in vascular and endothelial injury and ischemia.

Dr. Michael Har-Noy concludes that presenting tumor antigens in an environment of inflammation can impedes tumor cells’ ability to evade immune attack.  Early results show that CryoStimTM is effective against many different malignancies.

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Dr. Michael Har-Noy’s Unique Anti-tumor Technology

“Cancer is a horribly debilitating condition that affects many million people worldwide” says Dr. Michael Har-Noy, founder of Immunovative Therapies Ltd.   About 40% of the population will get sometime in their life.  There are over one million new cancer diagnoses each year.  The crippling effects of cancer work their way into every part of a patient’s life, as well as those of their loved ones.  Cancer is so hard to treat because it usually produces no symptoms until it is very advanced, and when it is discovered it has usually progressed beyond the point where it can be cured using conventional means.  Surgery, chemotherapy, and radiation cannot kill every tumor cell.

Dr. Michael Har-Noy founded Immunovative Therapies, Ltd., in 2004 in Israel.  The company grew out of the Misgav Venture Accelerator in Israel and was given a $300,000 grant by the Office of the Chief Scientist.  Dr. Michael Har-Noy and his staff are designing unique immune treatments that may alter cancer therapy permanently.

Dr. Michael Har-Noy says that most immunotherapies fall short for two reasons.  First, they augment the wrong immune response, namely the patient’s own response that has already failed to eliminate the cancer.  Secondly, they fail because they can’t disable the cancer’s ability to hide itself from the created immune response.

Dr. Michael Har-Noy has engineered a totally different approach to the treatment of cancer – a process he has termed the “Mirror EffectTM”.  This effect involves re-creating the successful immune response of an allogeneic bone marrow transplant without the toxic graft-versus-host side effect   “Dr. Michael Har-Noy’s preliminary testing of his unique drugs has demonstrated remarkable results in several different cancers.  Dr. Michael Har-Noy indicates that AlloStimTM’s efficacy against KRAS gene positive metastatic colon cancer will soon be tested in a randomized study.