re: mechanism of action of StressGen's "CoVal" platform.
"CoVal" is Stressgen's marketing term for it's therapeutic vaccine platform of two proteins COVALently combined into one protein dissolved in saline and injected sub-cutaneously 3 times over 2 months.
One of the two proteins is bacterial heat shock protein which Stressgen in the past has said confers visibility to the immune system. The second protein is a tumor-specific antigen. The antigen protein is said to give killer T cells a target to search for. The disease condition goes away when the killer T cells destroy all cells containing the target.
The following press release,
newswire.ca
"Stressgen announces presentation of data on the mechanism for the immunotherapeutic activity of HspE7 at HPV 2002"
states that the innate immune system cells are alerted, send signals to the adaptive immune system, which activates killer T cells. The PR states that a "specific receptor" is involved.
The following abstract,
stressgen.com
"A mechanism for the immunotherapeutic potential of HspE7: Integration of innate and adaptive immunity."
identifies the receptor as Toll-like Receptor 4 (Tlr-4)
Toll-like Receptor research is HOT, HOT, HOT. The last 2 years has seen a ton of papers in this area.
Stress proteins are hundreds of millions of years old and human genes could well encode an innate sensitivity to them. The different TLRs are receptors for an array of germline-encoded microbial products, including lipopolysaccharide (LPS) from gram-negative bacteria. Tlr-4, a member of this family of pathogen-associated pattern recognition receptors, has been shown to be sensitive to heat shock proteins.
The sub-cutaneous injection of HspE7 is in the presence of macrophages and tissue dendritic cells. One ability of dendritic cells is macropinocytosis, whereby quantities of extracellular material are taken up in a single vesicle. The Human Papilloma Virus E7 antigen could thus be introduced to the dendritic cell.
The dendritic cell Tlr-4 receptor can detect the heat shock protein in the HspE7 and begin a well-known signaling pathway involving TIR, MyD88, SIIK, TRAF6, I(kappa)k, I(kappa)B, and finally NF(kappa)B. The transcription factor NF(kappa)B enters the nucleus of the dendritic cell and activates genes. As a result, the dendritic cell migrates to the nearest lymph node and has gained the ability to stimulate T cells.
Newly targeted T cells go forth kill all cells they perceive to contain the E7 protein from Human Papilloma Virus and therapeutic benefit results.
Heat. |
