Danger Signals

The Mirror Effect® takes advantage of “danger signals” to provide adjuvant support to promote cellular immune response cascades, antigen-presenting cell maturation and conditioning of microenvironments to reverse immune suppression and create conditions for in-situ vaccination. Immune responses are triggered by “danger signals,” or “alarm signals,” released by the body's own cells. 

AlloStim® living immune cells are foreign to the body and are rejected by the host immune system shortly after administration. The rejection of AlloStim® and the subsequent lysing of tumors (or viral infected cells) releases damage-associated molecular pattern molecules (DAMPs).  DAMPs, are molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the immune and inflammatory response. DAMPs vary greatly depending on the type of cell (epithelial, mesenchymal, etc.) and injured tissue. Mirror Effect® rejection DAMPs include heat-shock proteins (HSP) with chaperoned alloantigens, high-mobility group box 1 (HMGB1) and cytokines including the interferons. Non-protein DAMPs including ATP, uric acid, heparin sulfate, and DNA can also be released.

DAMPs released after AlloStim® rejection caused the local dendritic cells which process the released HSP to mature to DC1. This initiates a cascade which activates both innate and adaptive immune mechanisms that result in lysis of tumor or viral infected cells.  This first wave of lysis acts by a combination of various mechanisms to condition the microenvironment causing formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes.

The rejection of AlloStim® in the skin activates innate immune responses to create a local immuno-competent environment at the injection site.  Combining a disease antigen at the local site or at the site of tumor cell ablation can create conditions for enhancement of in-situ vaccination.

Intravenous AlloStim® causes a rejection response in the circulation which results releases of DAMPs in the  plasma.  Plasma DAMPs are responsible for causing alarms which turn off a tumor’s ability to suppress and evade immune attack, permitting immune elimination.