Our Technology
Introduction
Our Mirror Effect® technology platform was developed from an advanced understanding of the multiple regulatory pathways involved in anti-tumor and anti-pathogen immunity, as well as the immune mechanisms used by tumors and viruses to suppress immune responses and avoid immune elimination. We apply this advanced knowledge of immune mechanisms to the development of products and design of protocols using those products which ‘mirror’ proven effective immune mechanisms and then imprint these effective mechanisms over resident failed immune responses.
The “Mirror Effect®” enables us to use an “off-the-shelf” drug to custom design a beneficial immune response resulting in patient-specific, disease-specific immunity. We use our patented AlloStim® living cell drug as a tool for mirroring immune mechanisms. We currently have five next generation Mirror Effect® clinical vaccine protocols, reverse engineered from proven therapeutic immune mechanisms, in clinical development called: StimVax®, CryoVax®, AlloVax®, AlloPrime® and AlloLife®.
First generation immunotherapy products, such as checkpoint inhibitor drugs and CAR-T cell therapies, have demonstrated significant survival improvements in some patients with certain immunogenic cancers. However, primary and acquired/secondary resistance to immunotherapy remains a challenge for expanding the indications and the response rates of these first generation immunotherapy drugs. There are also significant technical issues which inhibit the expanded commercial use of first generation immunotherapy drugs. We have developed next generation immunotherapy vaccines based on our Mirror Effect® platform technology. Our next generation vaccine products overcome the technological challenges faced by first generation immunotherapies.
Mirror Effect
Next Generation Vaccines
®
Our Mirror Effect® vaccines imprint both preventive and therapeutic immunity against cancer and infectious disease upon the immune system of patients. The unique feature of our vaccines is that we use an “off-the-shelf” living immune cell drug that is used in different patients with different diseases and yet results in a patient-specific, disease-specific customized immune response against the disease of each individual patient through a “in-situ vaccination” mechanism, which is a vaccination that occurs inside of the body.
The ultimate goal of immunotherapy is to train the immune system to identify and completely eliminate tumors and viral infected cells (“sterilizing immunity”) and then ‘remember’ the eliminated tumor or virus. With immune memory, if ever the tumor or virus returns, a pre-programmed immune response is primed and ready to eliminate the disease without further treatment. First generation immunotherapy drugs, such as checkpoint inhibitors and CAR-T immunotherapies do not incorporate this type of mechanism.
The only technology capable of educating the immune system to elicit sterilizing immune responses and immune memory is vaccine technology. However, the goal of developing vaccines to prevent disease or used as treatments for diseases such as cancers and modern viral infections has remained elusive for decades. Our Mirror Effect® technology is a significant breakthrough for developing effective vaccines for cancer and modern viruses.
Our Mirror Effect® platform technology represents a completely novel approach to the design and clinical translation of immunological mechanisms into vaccines for the treatment and prevention of disease. No one else does it like we do. We have over 200 issued patents covering our novel protocols, products and methods.
Vaccines are designed to educate the immune system through the encounter with samples of a pathogen or with cancer. All vaccine designs have certain common challenges, such as what antigen and what adjuvant to use, what type of immune response to generate and how to make the immune response long lasting. Cancer and some viruses, additionally, present several unique hurdles. Cancer vaccines must overcome immune suppression that is: exerted by the tumor; by previous therapy; and, by the effects of advanced age. Viral and cancer vaccines must also address the various ways that these diseases have evolved to evade immune recognition and elimination.
Characteristic Of Our
Novel Mirror Effect® Vaccines
Learn more about the science and significance of these features of a Mirror Effect® vaccine:
Novel Allogeneic
Immune Cell Therapy
Our technology is based upon a novel allogeneic cell therapy model using a patented “off-the-shelf”, non-genetically-manipulated, living immune cell called “AlloStim®”. In contrast to autologous immune cell therapy models that incorporate living immune cells first isolated from a patient, activated and expanded outside the body, and then re-infused to the patient in order to provide anti-tumor effects (e.g.,CAR-T cells, NK cells, TIL cells and dendritic cells), AlloStim® immune cells are differentiated and expanded from precursor cells purified from the blood of healthy donors and administered to unrelated patients (allogeneic).
The allogeneic immune cell therapy business model has commercial advantages over the autologous immune cell model. Our allogeneic immune cell model is different from other allogeneic cell models under development. Current allogeneic immune cell therapies derive treatments for multiple patients from the cells of either a single donor, cell line or stem cell. In all these prior cases, the allogeneic cells that are infused are intended to perform the desired immune effector functions (e.g., killing tumor cells, suppressing inflammation, etc.). The administration of these current allogeneic cell therapies have only transient effects as they are eventually rejected by the host, neutralizing the effects of the therapy.
Many allogeneic therapies require chemotherapy or other immunosuppressive therapy prior to cell transfer in order to delay rejection. In some cases, the persistence of the allogeneic cells can also cause severe side-effects, such as graft vs host disease (GVHD) requiring additional elaborate genetic engineering to overcome.
Uniquely, our mis-matched AlloStim® cells are intentionally designed to be rejected by the patient’s immune system within 24h of administration. Rather than perform the direct effector function, such as killing tumors, the rejection of AlloStim® modulates the host immune system to perform effector functions. This enables maintenance of long-term effects on the host immune system despite early rejection.
Autologous Immune Cell Therapy
The patient-specific nature of autologous cell therapies can make large-scale production extremely challenging because a separate batch must be produced for each patient. An error in the production directly translates into a failed treatment for a patient. When the source cells are derived from seriously ill patients, the risk of manufacturing failure increases.
Allogeneic Immune Cell Therapy
Allogenic immune cell therapies provide the advantage of an economy of scale and “off-the-shelf” distribution capability. However, allogeneic cell therapies have a narrow window of effectiveness as they are readily rejected by the host immune system. The rejection of AlloStim® cells modifies the host immune system in a manner that provides long lasting effects.
AlloStim® cells do not directly mediate immune effects such as killing tumors, they instead act to modulate and remodel the host immune system. This unique feature of AlloStim® distinguishes our cell therapy from all current autologous and allogeneic cell therapies currently in clinical use or under development. The rejection of AlloStim® causes changes to the patient’s own resident immune cells, so they become capable of orchestrating a cascade of immune events which result in immune protection against existing disease or preventing disease. The immune modulating effects of AlloStim® rejection are able to be used to elicit effective immune responses against cancer and pathogens and to re-model weakened immune systems, such as those of the elderly, that fail to protect against cancers and pathogens.
Reverse Engineering
Immune Effector Functions
Our “Mirror Effect®” technology is a novel process for custom designing new, effective immune responses in people that can be imprinted upon and dominate over a resident non-effective immune response. The Mirror Effect® process begins with mapping the cascade of immune events which occur in space and time that result in a desired immune response outcome. The immune response of a patient with disease is then similarly mapped in order to understand how the disease was able to change and evade an effective immune response. From this information, combined with the knowledge of the various immune effects that can be elicited by differing the dosing, frequency of dosing and route of dosing of AlloStim®, custom protocols are developed.
Immune Mechanism
Healthy young immune response to respiratory viral infection. Clears virus without progression to serious symptoms
Allogeneic stem cell transplantation (“mini-transplant”) anti-tumor mechanism. Capable of killing chemotherapy-resistant tumors.
Chronic inflammation has been correlated with diseases of old age; such as cancers; cardiovascular diseases, such as arthrosclerosis; and, neurological diseases, such as Alzheimer’s Disease and Parkinson’s disease.
Protocols
StimVax®
AlloVax®
CryoVax®
metastatic solid tumors
AlloPrime®
Programs rapid innate anti-viral response
AlloLife®
Reverses chronic inflammation
Our StimVax® protocol reverse engineers the Mini-Transplant anti-tumor mechanism
Our AlloVax® and CryoVax® protocol reverse engineers the abscopal effect and combines with the Mini-Transplant anti-tumor mechanism
Our AlloPrime® protocol reverse engineers the early innate antiviral immune response of the young
Our AlloLife® protocol reverse engineers the innate immune response that eliminates the sources of chronic inflammation.
StimVax®: Reverse Engineering The Mini-Transplant Mechanism
The anti-tumor immune mechanism that occurs after “Mini-Transplant” procedures is known as the “Graft vs. Tumor” effect or GVT. GVT has been described as the most powerful anti-tumor effect ever discovered, as this mechanism is the only mechanism known to overcome tumor immune-evasion strategies and cause the elimination of chemotherapy-resistant metastatic tumors. The GVT mechanism can be evoked after stem cells from a tissue-type matched healthy donor are transplanted into a cancer patient (host), creating a “chimeric” immune system that is part host and part donor (donor=graft). In order to create a chimeric immune system, a host must first be treated with chemotherapy, not for the purpose of killing the tumor, but for the purpose of suppressing the immune system sufficient to prevent the rejection of the transplanted foreign cells. Since the doses of chemotherapy required to suppress the immune system in order to create a chimeric immune system are less than the doses required to kill tumors, the procedure has been called a “Mini-Transplant”. Mini-transplant procedures have been used successfully to treat a variety of cancer types, however the clinical use has been limited due to the often lethal side-effect known as graft vs. host disease (GVHD) that is associated with these procedures.
Mini-Transplant: The Beautiful & The Ugly
Panel A
Before
After
Panel B
Skin
Panel A is a CT scan of the liver of a breast cancer patient before and after Mini-Transplant. Before there are multiple metastatic lesions (in the red circles) within the liver. After Mini-Transplant, all the tumors have been eliminated. However, while the tumors have been eliminated, Panel B shows how the immune system has attacked the skin (GVHD). The same attack occurs on the linings of the intestines, literally eating the patients from the inside and the outside. The Mini-Transplant GVT mechanism often clears the tumors, but more often GVHD kills the patient.
Researchers around the world have tried unsuccessfully to separate the beneficial GVT effect from the detrimental GVHD toxicity. The immune mechanisms are inter-related and proportional such that anything that is done to suppress GVHD, also suppresses the GVT effect. Similarly, anything that is done to enhance the GVT effect also enhances GVHD toxicity.
Recognizing the intimate and proportional relationship of the GVT and GVHD effects that occur after Mini-Transplant procedures and the history of unsuccessful attempts to separate GVT from GVHD, Mirror Effect® technology provided a breakthrough approach to this problem. Instead of attempting to separate GVT from GVHD as others have done, the Mirror Effect® proposed to maintain the intimate relationship between the two effects, but reverse the immunological flow. In Mini-Transplant, the immunological flow cascades from the graft to the host, causing GVT and GVHD. Whereas in the Mirror Effect®, the flow originates from the host creating a non-toxic Host vs. Graft (HVG) rejection effect (the ‘mirror’ of GVHD) which supports a host vs. tumor (HVT) effect (the ‘mirror’ of GVT). The HVT effect elicited by the Mirror Effect® mechanism is equally as powerful as the GVT effect of Mini-Transplant.
Panel A is a CT scan of the liver of a breast cancer patient before and after Mini-Transplant. Before there are multiple metastatic lesions (in the red circles) within the liver. After Mini-Transplant, all the tumors have been eliminated. However, while the tumors have been eliminated, Panel B shows how the immune system has attacked the skin (GVHD). The same attack occurs on the linings of the intestines, literally eating the patients from the inside and the outside. The Mini-Transplant GVT mechanism often clears the tumors, but more often GVHD kills the patient.
The GvT/GvHD effects only occur when a patient is pre-treated with chemotherapy, not to kill the tumor, but to suppress the immune system sufficient to enable the engraftment of the cells from a matched tissue donor. Only when there is engraftment of foreign immune cells (chimeric immune system) does the rejection of the cells cause an anti-tumor effect. Infusion of allogeneic immune cells without prior chemotherapy conditioning does not elicit an anti-tumor effect. The GvHD attack on normal cells, especially endothelial cells of the lining of the gut, causes the release of danger signals. These danger signals are responsible for supporting the GVT effect and breaking down the ability of the tumor to evade or suppress immune attack.
In order to eliminate the need for chemotherapy conditioning and matched tissue donors in the HvG/HvT mirror mechanism, AlloStim® cells are designed to release the same danger signals upon rejection as are released in GvHD.
The StimVax® protocol that is reversed engineered from the Mini-Transplant mechanism incorporates a natural in-situ vaccination mechanism supported by the danger signals released upon rejection of AlloStim®. Our other cancer vaccine protocols, AlloVax® and CryoVax® add an additional in-situ vaccination enhancing step that was reverse engineered from the abscopal effect that occasionally occurs after radiotherapy (RT).
The GVT immune response that occurs after Mini-Transplant is an example of a successful in-situ vaccination of an existing tumor resulting in tumor elimination. The successful in-situ vaccination occurs due to the adjuvant effect of ‘danger signals’ released after GVHD attack on normal tissues. This intimate relationship between GVT and GVHD has hindered the harnessing of the power of GVT to treat existing tumors. We engineered AlloStim® to release the same danger signals as are released when normal cells are killed by GVHD. Thus, we are able to create the conditions needed for an in-situ vaccination effect on existing tumors without GVHD toxicity.