Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd., says that the “Mirror EffectTM” is a proprietary immunologic treatment that has finally been able to separate the beneficial graft versus tumor (GVT) response of an allogeneic bone marrow transplant (BMT) from the deadly graft versus host (GVHD) complication. The separation of the GVT and GVHD processes has been called the “Holy Grail” of cancer treatment.
Dr. Michael Har-Noy tells us that the answer was to design a T-cell infusion that would mimic the immunologic responses caused by the transplanted donor cells but that would be ultimately controlled by the patient’s own immune cells. This proprietary response, termed the “Mirror EffectTM”, could theoretically produce the curative response of a BMT without the lethal complication of GVHD.
Dr. Michael Har-Noy says that the Mirror EffectTM process reverses the intimately related GVT and GVHD mechanisms that arise from the infused donor cells. This effect thus arises from the host immune response rather than from the transplanted cells, thus precipitating a host versus tumor (HVT) response that is associated with the non-toxic host versus graft (HVG) rejection process. To initiate the Mirror EffectTM reaction, T-cells from a normal donor are infused into a cancer patient. Dr. Michael Har-Noy says that these infused cells prompt the patient’s immune response to attack the malignant cells (HVT effect) and create an extremely inflammatory environment which incapacitates the tumor’s ability to evade the patient’s immune response.
Dr. Michael Har-Noy says that since the HVT response must be linked to a HVG rejection mechanism, the patient needs have an intact immune system that can rise up and reject the donor T-cells. Additionally, since graft rejection (HVG) is the desired response, the donor cells are also ideally intentionally mismatched to the recipient. Dr. Michael Har-Noy says that this is a vital and much-needed advancement over allogeneic BMT treatments, where only one third of potential recipients have a suitably matched donor.
The Mirror EffectTM, notes Dr. Michael Har-Noy, therefore involves the infusion of intentionally mismatched donor cells into a cancer patient that has received no pretreatment. The infused cells are then rejected by the patient’s immune system. This HVG rejection is the “mirror” of the deadly GVHD but has no toxicity. The HVG mechanism precipitates host-mediated tumor destruction (HVT), which is the “mirror” of the GVT process. Dr. Michael Har-Noy concludes that the Mirror EffectTM imitates the desired GVT effect of an allogeneic BMT while simultaneously avoiding the often-fatal toxicity of GVHD.
Dr. Michael Har-Noy feels that the Mirror EffectTM may be the beginning an entire new field of oncology. Please visit www.immunocare.net for more information on Dr. Michael Har-noy’s ongoing clinical trials.
Conventional cancer therapies, such as chemotherapy, surgery, and radiation, cannot target and destroy every metastatic cancer cell in a patient’s body. Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd, a biotech company in Israel, says that a patient’s natural immunity, if conditioned properly, may be able to do this. Dr. Michael Har-Noy indicates that if one could somehow condition a patient’s immune response so that it could find and eradicate malignant cells, an actual complete cure of the disease may be possible.
Over the past several years, Dr. Michael Har-Noy has developed a proprietary treatment he has termed the “Mirror EffectTM. The Mirror EffectTM technology is unique in that it both empowers a patient’s immune response to target malignant cells and disrupts the tumor’s ability to evade this response. The creation of the Mirror EffectTM and the development of the drugs that utilize it have the capacity to create an entire new field of oncology. Dr. Michael Har-Noy goes on to say that patenting and marketing these therapies could be both tremendously beneficial to cancer patients and immensely profitable for a company.
Dr. Michael Har-Noy has been working with his patent lawyers to construct a portfolio that protects the immense scope, depth, and detail of the Mirror EffectTM and outlines its use to condition a patient’s immune system to fight some of the most refractory conditions described in the medical literature. Dr. Michael Har-Noy notes that the patent portfolio he is creating entails not only protection of his company’s drugs and synthesizing methods but also has the potential to spawn an entirely new industry based on manipulating the human immune response.
Ultimately, Dr. Michael Har-Noy’s patent portfolio will probably start a new field of oncologic therapy and radically alter the way malignancies are treated. Patent attorneys have compared potential impact of Dr. Michael Har-Noy’s portfolio to that of the double-clicking of a mouse on a user interface on a computer screen. This double-clicking technology formed the foundation of the multi-billion dollar internet advertising industry. Dr. Michael Har-Noy believes his new technology will introduce an entirely new field of oncology and forever change the way cancer is treated, and that his Mirror EffectTM idea will therefore prove to be of virtually limitless value.
Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., indicates that the that the immune cascade precipitated by an allogeneic stem cell transplant has been shown to be efficacious in eradicating chemotherapy-resistant metastatic tumors in spite of their immunoavoidance mechanisms, but this beneficial immune response is closely linked to lethal graft versus host disease (GVHD) toxicity and is therefore limited in clinical sue.
Dr. Michael Har-Noy has engineered the unique compound AlloStimTM that is designed to create a host anti-tumor response without causing the potentially lethal GVHD side effect. Dr. Michael Har-Noy says that AlloStimTM has been preliminarily tested in an FDA-approved phase I/II study involving 42 late-stage metastatic cancer patients with solid tumors of various different cell types. Dr. Michael Har-Noy indicated that most of the study patients demonstrated evidence of improved survival and exhibited immune-mediated killing of malignant cells without GVHD toxicity. Conventional RECIST criteria tended to overestimated tumor size because responding masses swelled and appeared to increase in size on computed tomographic scan.
Dr. Michael Har-Noy notes that serum interleukin 12 (IL-12) levels seemed to predict improved survival. Fifty percent of the study patients treated with AlloStimTM were positive for IL-12 and survived a median of 211 days, as compared with a median longevity of 131 days for IL-12 negative patients. Nine of 16 patients with refractory metastatic breast tumors were positive for IL-12. Dr. Michael Har-Noy noted that the subset of five HER2+ breast cancer patients all manifested IL-12 positive and had a median survival of 416 days. In contrast, the 11 HER2- study patients had a median survival of only 134 days; four of these eleven patients were IL-12 positive.
Dr. Michael Har-Noy indicates that HER2+ breast cancers are usually very aggressive and have a much worse prognosis than their HER2- counterparts. The superior response to AlloStimTM of the HER2+ breast cancer study patients could be due to the high levels of anti-HER2 antibodies that they exhibit. Dr. Michael Har-Noy concludes that the AlloStimTM therapy likely augments the ability of these anti-HER2 antibodies to destroy malignant tissue.
This preliminary report describes dramatically improved survival in a gravely ill subset of cancer patients with a very short life expectancy. Dr. Michael Har-Noy is planning to undertake a randomized, double blind Phase II/III study of AlloStimTM in patients with metastatic breast cancer.
Dr. Michael Har-Noy, CEO of Immunovative Therapies, Ltd. says that the failure of hundreds of immunotherapy clinical studies to produce meaningful anti-tumor treatments calls for a re-evaluation of their underlying theories. For more than 200 years, scientists have successfully used vaccines to prevent many infectious diseases by inducing a humoral antibody response. Dr. Michael Har-Noy notes that researchers have attempted to apply the same ideas in developing vaccines to treat existing cancers, despite the fact that vaccines giving protection against pathogenic infections cannot eradicate existing infections caused by the same pathogen. Therefore, notes Dr. Michael Har-Noy, the modeling of these cancer therapies is fundamentally flawed, because protective immunity does not provide therapeutic immunity.
Dr. Michael Har-Noy indicates that a specific cellular immune response is required to provide therapeutic immunity from cancer. Researchers have followed conventional strategies in cancer vaccine creation by attempting to find unique tumor-specific antigens (TSA) not found on normal cells, or by looking for tumor-associated antigens (TAA) overexpressed by malignant cells. Dr. Michael Har-Noy says that TSAs have only been found in cancers caused by infectious agents, such as EBNA-1 antigen from Epstein Barr virus-induced Burkitt’s lymphoma. However, TAAs have been identified in most cancers forming in immunocompetent patients. Furthermore, says Dr. Michael Har-Noy, many malignancies have a significant inflammatory component which includes a widely varied leukocyte infiltrate of neutrophils, macrophages, mast cells, and eosinophils, frequently associated with lymphocytes. Human cancers are usually densely infiltrated with immune cells – a fact arguing against inadequate tumor antigen recognition.
Dr. Michael Har-Noy notes that previous attempts to enhance patients’ immune responses have accelerated rather than slowed tumor growth. Therefore, he says, the notion that cancers are “invisible” to the immune system, which thus needs to be augmented, is misconceived. Dr. Michael Har-Noy thinks that the problem is that the patient’s immune response to the tumor, while strong, may be the wrong kind. It is therefore not surprising that tumor growth may be enhanced rather than suppressed by attempting to strengthen an immune response that has already failed to protect against cancer growth. Dr. Michael Har-Noy notes that this misconception is the basic flaw in the conventional strategy of cancer vaccine research.
Dr. Michael Har-Noy is conducting a Phase I/II trial of his CRCL vaccine in Bangkok, Thailand. Please visit www.immunocare.net for more information.
Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., says that tumor-derived chaperone-rich cell lysate (CRCL), which is composed of various heat shock proteins, has been successfully used to produce tumor-specific T-cell responses and protective immunity against a wide variety of murine tumors. Dr. Michael Har-Noy says that investigators have also examined the ability of CRCL derived from human ovarian cancer cells to activate dendritic cells and to stimulate the production of in vitro tumor-specific T-cells.
CRCL was produced from ovarian tumors and the SKOV3-A2 ovarian cancer cell line. Dr. Michael Har-Noy noted that peripheral blood mononucleocytes from both HLA-A2+ healthy donors and HLA-A2+ ovarian cancer patients were stimulated every week with autologous dendritic cells heavily laden with CRCL derived from ovarian tumor cells. Following four to six in vitro stimulations, cytokine secretion and cytotoxicity were specifically measured.
Dr. Michael Har-Noy noted that CRCL stimulation increased the amount of interleukin (IL)-12 secretion and augmented the immune-stimulatory ability of the dendritic cells. Also, T-cells from healthy controls and from patients with ovarian cancer both secreted larger quantities of interferon-g after in vitro re-stimulation with ovarian cancer-derived CRCL than after stimulation with HER2/neu or WT1 peptide-pulsed dendritic cells.
Dr. Michael Har-Noy points out that the investigators were able to generate cytotoxic T-lymphocyte activity against cancer specific antigens from all of healthy donors, but from only 25% of the patients with advanced ovarian cancer in the absence of CRCL stimulation. Dr. Michael Har-Noy concludes that these results further substantiate the idea that CRCL will likely be an effective treatment for women suffering from ovarian cancer and that this individualized vaccine will yield promising new approaches for cancer immunotherapy.
Dr. Michael Har-Noy is now conducting a Phase I/II trial of the CRCL vaccine in various solid tumors. He is conducting the study in Bangkok, Thailand, and has combined it with a Compassionate Use program. Dr. Michael Har-Noy indicates that detailed information can be found at www.immunocare.net.
At the 2012 ASCO Annual Meeting, Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., presented remarkable survival data a subgroup of HER2+ breast cancer patients.
Dr. Michael Har-Noy states that the immune response resulting from an allogeneic stem cell transplant has been effective in killing resistant metastatic cancer cells despite the tumor’s immunoavoidance abilities, but that this immune response is closely linked to the lethal graft versus host disease (GVHD) and is thus of limited clinical use.
Dr. Michael Har-Noy has developed a unique compound, AlloStimTM which was formulated to stimulate a host anti-tumor response while avoiding GVHD toxicity. Dr. Michael Har-Noy describes how AlloStimTM was recently tested in an FDA-approved phase I/II trial involving 42 late-stage metastatic cancer patients with a variety of tumor types. Most patients in the trial experienced prolonged survival and immune-mediated tumor lysis without suffering GVHD toxicity. Conventional RECIST criteria tended to overestimated tumor size, as responding masses swelled and appeared to grow bigger on computed tomographic scan.
Dr. Michael Har-Noy noted that serum interleukin 12 (IL-12) levels were identified to be a consistent predictor of improved survival. Half of the study patients were IL-12 positive and survived a median of 211 days. In contrast, the IL-12 negative subjects lived a median of 131 days. Nine of 16 metastatic breast cancer patients in the study group were IL-12 positive. The HER2+ subset of five breast cancer patients were all IL-12 positive and had a median survival of 416 days, while the median survival of the eleven HER2- patients was only 134 days. Dr. Michael Har-Noy noted that HER2+ tumors metastasize more quickly and have a poorer prognosis then their HER2- counterparts. The remarkable response to AlloStimTM in the HER2+ metastatic breast cancer patients could result from high quantities of anti-HER2+ antibodies exhibited by this patient subset. Dr. Michael Har-Noy adds that the allogeneic cell treatment may augment the ability of these antibodies to destroy the cancer cells.
Please read the abstract on the official ASCO website by clicking here. Dr. Michael Har-Noy is conducting further trials of his unique drugs in Bangkok, Thailand. He is planning a pivotal Phase II/III trial of AlloStimTM in the treatment of refractory breast cancer. For more information, please visit www.immunocare.net.
Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd., says that the “Mirror EffectTM” is an immune mechanism that separates the beneficial graft versus tumor (GVT) effect of an allogeneic bone marrow transplant (BMT) from the often-lethal graft versus host disease (GVHD) side effect.
Dr. Michael Har-Noy separated these two immunologic events by creating a T-cell infusion that simulated the immune reactions caused by the transplanted donor cells but that was controlled by the patient’s own immune cells. He says that this process, termed the Mirror EffectTM, can theoretically reproduce the curative treatment of a BMT without exposing the patient to potentially the life-threatening complication of GVHD.
Dr. Michael Har-Noy indicates that Mirror EffectTM mechanism reverses the intimately related GVT and GVHD reactions stemming from the infused graft cells. This effect originates from the patient’s own immune system instead of from transplanted cells, thereby creating a “host versus tumor” (HVT) response associated with the non-toxic host versus graft (HVG) rejection mechanism. Dr. Michael Har-Noy says that in order to precipitate the “Mirror EffectTM”, T-cells from a normal donor are infused into a cancer patient. These donor T-cells then stimulate the patient’s own immune response to attack the cancer (HVT effect) and create an inflammatory environment which incapacitates the tumor’s immunoavoidance capabilities.
Dr. Michael Har-Noy indicates that since the HVT response must be linked to a HVG rejection, the patient must have an intact immune system that can mount a response to reject the donor T-cells. Additionally, since graft rejection (HVG) is desired, the donor cells need to be mismatched to the patient. This aspect of the treatment is a marked improvement over allogeneic BMT procedures, where only 33% of recipients have a suitably related donor.
The Mirror EffectTM, says Dr. Michael Har-Noy, therefore involves infusion of mismatched donor cells into a cancer patient that has not been pretreated. These infused cells are then rejected by the patient’s immune system. This HVG reaction is the “mirror” of the lethal GVHD mechanism but is non-toxic. Dr. Michael Har-Noy adds that the HVG rejection precipitates host-mediated tumor lysis (HVT), which is the actual “mirror” of the GVT process. The Mirror EffectTM thus imitates the curative GVT effect of an allogeneic BMT while simultaneously avoiding the often-lethal GVHD .
Dr. Michael Har-Noy feels that the “Mirror EffectTM” may spawn an entire new field of cancer treatment. For more information about Dr. Michael Har-Noy’s ongoing clinical trials and Compassionate Use program, please visit www.immunocare.net .