In-Situ Vaccination

Mirror Effect® protocols use an “off-the-shelf” immunotherapy drug, AlloStim®, derived from healthy blood donors that can be administered to patients without need for tissue type match.  Despite the same drug being administered to many different people, each with different diseases, the result is a customized  immune response directed against the individual patient’s own cancer or infectious disease.  This is a unique feature of Mirror Effect® technology.

To accomplish this unique mechanism, Mirror Effect® protocols takes advantage of an immunological mechanism known as “in-situ vaccination”.  This is a vaccination that occurs inside the body.  An in-situ vaccination occurs when antigens found inside of cells are released from lysed tumors or viral infected cells into the local microenvironment under ’danger’ conditions which lead to the programming of a tumor-specific or viral-specific immune response. This type of immune response then leads to an immune-mediated eradication of tumors or viral infected cells through-out the body.   Once the body is “sterilized” from the disease, the immune system can remember the disease.  Upon disease recurrence, this memory enables a memory immune response to rise up to eradicate the tumor or pathogen without any further treatment, preventing a recurrence of disease.

In-situ vaccination occurs naturally as part of immune surveillance against cancers and viral infections, leading to early immune elimination before establishment of disease. However, the presence of disease is evidence of a failure of the natural in-situ vaccination mechanism.   In this failed mode, the immune system has been exposed to tumor or viral antigens, but then fails to generate an immune response capable of preventing disease. 

Current cancer and viral vaccine methods generally attempt to re-expose the same tumor or viral antigens to the same immune system that previously failed to elicit a response  to these antigens which prevents disease.   This is seen as a major technological flaw in the design of therapeutic vaccines.

Therefore, when existing disease is present, the technological challenge is not to re-expose, as is currently done, but to re-program an effective immune response.  Re-programming such that upon re-exposure to the same disease antigens that previously failed to provide a protective immune response results in a different immune response.  Once the immune response has been re-programmed, it is then important that the new re-programmed immune response to the disease antigens dominate over the existing resident failed response.  Mirror Effect® technology is designed to address these requirements.

The Mirror Effect® creates in-situ vaccination by combining endogenous heat shock proteins (HSP), which chaperone tumor neoantigens or viral antigens, combined with AlloStim® and danger signals, providing the conditions necessary for creating in-situ vaccination:

We have reverse engineered several protocols which have an in-situ vaccination step to produce a patient-specific, disease-specific immune response.  All protocols at the vaccination step combine endogenous HSP chaperoned neoantigens with AlloStim® providing the adjuvant.

The StimVax® protocol vaccination step causing release of endogenous HSP through activation of NK cells which cause immunological tumor death by necrosis.

The CryoVax® protocol vaccination step causes release of endogenous HSP occurs through the ablation of a tumor lesion using extreme cold (cryoablation) or through extreme heat (radiation). The AlloVax® protocol isolates HSP from a tumor biopsy sample and injects together with AlloStim®.

The in-situ vaccination mechanism requires the combination of immunogenic cell lysis (necrosis), caused the disruption of cell membranes and the release of the internal contents into the surrounding microenvironment, and the presence of ‘danger signals’.  In Mirror Effect® protocols, the lysis of cells can be mediated by activated natural killer (NK) cells, ablation using extreme cold (cryoablation) or by high energy radiation (unfractionated).   The danger signals are provided by AlloStim® cells serving as an adjuvant.  When local antigen presenting cells, such as dendritic cells, engulf and process the released heat shock proteins (HSP), which chaperone the neoantigens from the lysed cells, in the presence of danger signals released from AlloStim®, these are the conditions that create the environment for in-situ vaccination.

In-situ vaccination does not require the knowledge of specific disease antigens or epitopes.  In this manner, a person’s own immune system can select the epitopes that likely vary person-to-person.  Whatever the tumor type or virus type, whatever mutations or changes that occur in the body or in the population, in-situ vaccination provides immunity specific for the resident disease, even when we don’t know about the structure of the disease antigens.