Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., a biotechnology company in Israel, says that immunotherapy has not always been accepted as having a high potential to successfully treat cancer. Immunotherapy was widely reported to be a potential cure for cancer in the late 1980's. Dr. Michael Har-Noy notes that this publicity motivated many companies to invest in various immunotherapy approaches throughout the late 1980's and early 1990's. During the early 2000's, much of the research done involving immunotherapy was publicized and was highly disappointing. Many high profile failures of early immunotherapy approaches in late stage clinical trials tainted the oncology community and scared off many large venture capital firms. Dr. Michael Har-Noy notes that it was widely accepted in these circles that immunotherapy was not suitable for treatment of cancer and had no real future in the treatment of the disease. Scientists thought that immunotherapy had very weak, if any, activity against cancer. Therefore, says Dr. Michael Har-Noy, it was thought that the only chance immunotherapy had to enter clinical practice was to treat minimal residual disease. However, the drug development process for new classes of drugs requires activity in late stage disease where no treatment options exist prior to testing earlier in the disease process. This combination of events, says Dr. Michael Har-Noy, resulted in very little investment and advancement of immunotherapy into the 2000's. Later, success with monoclonal antibodies and checkpoint inhibitors rekindled the enthusiasm for immunotherapy. Today, says Dr. Michael Har-Noy, cancer immunotherapy is a multi-billion dollar industry and likely represents the future of cancer treatment.
Dr. Michael Har-Noy of Immunovative Therapies, Ltd. says that checkpoint Blockade drugs block a molecule that cancer cells use to turn off immune cells that are armed and ready to kill. Yervoy blocks a molecule called CTLA-4 and Opdivo blocks a molecule called PD-1. When these molecules are blocked, immune cells are no longer blocked from killing the cancer. However,Dr. Michael Har-Noy notes that this mechanism works only if there is an existing immune response that is capable of killing the tumors.
Most cancer patients have not developed an effective immune response. For this reason, the response rates of checkpoint blockade drugs have been low or restricted to tumors that are highly immunogenic (such as melanoma). Dr. Michael Har-Noy has developed a novel technology that may serve as a platform to treat virtually all types of cancer and infectious diseases. This technology is different from previous immunotherapies that have failed clinically. Instead of being developed first in animals and then translated to humans, Dr. Michael Har-Noy's unique technology was reverse engineered from a human immune mechanism that has already been shown to be capable of killing chemotherapy-resistant metastatic cancers and that has been curative in many cases.
The immune effect that occurs after transplant of another person's immune cells (adult stem cells) into a cancer patient has been described as the most powerful anti-tumor mechanism ever discovered.Dr. Michael Har-Noy notes that this mechanism known as the “graft vs. tumor” effect or “GVT” is the only known mechanism for killing or debulking of chemotherapy-resistant metastatic disease. However, the clinical application of the GVT effect is severely limited due to an often lethal side-effect called “graft vs. host disease” or “GVHD” which is intimately associated with the GVT mechanism. The separation of the beneficial GVT effect from the detrimental GVHD effect has been described as the “holy grail” of transplantation research.
Dr. Michael Har-Noy has developed a drug named AlloStimTM which uses a patented “Mirror EffectTM” technology to create the curative effect of a transplant without the toxic GVHD.
Dr. Michael Har-Noy, CEO of Immunovative Therapies, Ltd., says that chaperone-rich cell lysate (CRCL), which is made up of heat shock proteins, has been used to produce tumor-specific immunity against many murine cancers. Dr. Michael Har-Noy notes that scientists have described ovarian tumor-derived CRCL's ability to activate dendritic cells promote tumor-specific T-cell production.
CRCL was made from SKOV3-A2 ovarian tumor cells. Dr. Michael Har-Noy says that dendritic cells with ovarian cancer-derived CRCL were used weekly to stimulate peripheral mononucleocytes from both HLA-A2+ donors and HLA-A2+ ovarian cancer patients. Cytotoxicity and cytokine production were subsequently measured after four to six treatments.
Dr. Michael Har-Noy noted that CRCL stimulation increased both the immune-stimulatory capacity of the dendritic cells as well as interleukin (IL)-12 production. T-cells from normal controls as well as from ovarian tumor patients secreted increased amounts of interferon-g after re-stimulation with CRCL as compared with dendritic cell stimulation.
Dr. Michael Har-Noy observed that without CRCL stimulation, investigators were able to produce cytotoxic T-lymphocyte activity against cancer specific antigens in all of healthy donors but in only one fourth of the ovarian cancer patients. Dr. Michael Har-Noy concludes that this substantiates the hypothesis that CRCL will effectively treat ovarian tumors and that this individualized vaccine will be a powerful new approach to cancer therapy.
Dr. Michael Har-Noy is now running a Phase I/II study of the CRCL vaccine in various solid malignancies. The study is being run in Bangkok, Thailand, and is combined with a Compassionate Use program.
Dr. Michael Har-Noy, CEO and founder Immunovative Therapies, Ltd., a biotechnology company in Israel, biotech company, talks about the preliminary results of an FDA-approved Phase I/II study in which 42 patients with different cancer types were treated with AlloStimTM combined with cryoablation. Dr. Michael Har-Noy will soon publish the study in a peer-reviewed journal.
This study was done in Carlsbad, California at one of Immunovative Therapies, Ltd.'s sister facilities. Dr. Michael Har-Noy noted that forty-two patients with different tumor types were enrolled. All patients had been previously treated with large amounts of radiation and/or chemotherapy and were expected to live only 60 days or less. The average age of the patients was 61 years; 90% had previous surgery, 45% had previous radiation, and all had previous chemotherapy. The cancer cell types were: 14 breast, three gallbladder, seven colorectal, three ovarian, three squamous cell, two sarcoma, two pancreas, two esophageal, two lung, two prostate, and one bladder. These severely ill subjects averaged 22.2 metastatic lesions and had an average ECOG (Eastern Cooperative Oncology Group) score of 2.2, indicating grave disability.
Dr. Michael Har-Noy indicated that the study group as a whole suffered few side effects from AlloStimTM. The most frequently encountered side effect was a flu-like condition that appeared within the first few days after treatment.
The mean survival of the study patients, says Dr. Michael Har-Noy, was 163 days – almost three times the predicted survival in untreated patients with similar tumors. Amazingly, 20% of the study group was still in remission one full year after treatment! Some patients lived for years after the trial's conclusion. This author is unaware of the exact longevity of all patients, but in general these survival statistics are far superior to anything that has yet been published.
Dr. Michael Har-Noy will soon publish these study results in a peer-reviewed. He says that these results must be viewed with caution, as this was only a preliminary, uncontrolled trial. He will soon undertake a Phase II/III, randomized double-blind controlled trial of AlloStimTM in patients with metastatic colon cancer.
Dr. Michael Har-Noy, CEO of Immunovative Therapies, Ltd. discusses how a 12-year-old Great Dane presenting with bronchoalveolar cancer, with a life expectancy 1 month or less, lived over 50 weeks post-diagnosis after being given Immunovative Therapies, Ltd.'s chaperone-rich-cell-lysate (CRCL).
Before treatment by Dr. Michael Har-Noy of Immunovative Therapies, Ltd., the Great Dane presented with nystagmus and collapse. Chest X-rays showed a lesion in the right lung. Ultrasound-guided needle biopsy demonstrated bronchoalveolar adenocarcinoma, and the canine underwent thoracotomy with lobectomy. The pathology analysis showed grade III bronchoalveolar adenocarcinoma with nodal metastases and blood vessel involvement. The average survival for this cancer is less than 1 month.
Using Dr. Michael Har-Noy's unique methods, a piece of the cancer was formulated into a CRCL vaccine, which was given weekly to the animal. Also, Imiquimod - a Toll-like receptor 7 agonist - was given to the animal for twelve treatments to stimulate Langerhans cells. Furthermore, the dog was given a single bacillus Calmette-Guerin shot at 30 weeks of treatment to further augment its immune mechanism.
The Great Dane remained good health until the cancer recurred during the 44th post-treatment week with Dr. Michael Har-Noy's CRCL compound. The dog then went on to have severe gastrointestinal bleeding and had to be euthanized at just beyond 50 weeks after the original diagnosis.
Dr. Michael Har-Noy indicates that this is the first report of significantly improved outcome following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a dog. This indicates that Dr. Michael Har-Noy's CRCL vaccine, when used with Imiquimod, is a safe and very efficacious therapy for canine malignancy.
Dr. Michael Har-Noy founded Immunovative Therapies Ltd. in Israel in 2004. Immunovative Therapies, Ltd. manufactures unique drugs that manipulate a patient's immune system and enable it to eradicate malignant cells.