Avid Bioservices Inc (CDMO)

[Protector]

biopharm, hasn't PPHM been there and didn't they have the T-shirt?

In the very beginning we had that story of cutting of bloodvessels to tumours.

Now with VEGF one seems to forget that it has TWO functions and not ONE. If someone will act on VEGF then it must be done in a way that angiogenesis is stopped but vascologenesis is NOT affected. Certainly in people (children to young adults till the age of about 21) that have non full grown vascular systems need vascologenesis for the formation of their vascular system.

And if angiogenesis is a feature of our bodies then that means it is NEEDED for something. It grows blood vessels starting from a vascular ancker-point. Hence one sees it start in the endothelial and make its way from there to form a network of blood-vessels of which the tumour can feed.

So VEGF therapies may PREVENT further extension (probably that wood have the good effect of slowing down or even stop tumour growth) but it would NOT clean up existing blood-vessels. However, if those existing blood-vessels would not get any oxygen anymore (and die off as a consequence because their oxygen supply is not restored) then blocking VEGF can help them OVERCOME absence of oxygen. Blocking that would indeed cut of supplies to the tumour.

NOW, why would I NOT be surprised that there is a PS-Receptor (one of the at least 10 identified on different cell types) that PREVENTS this blocking mechanisme as intended by Gabrilovich, from working? Very simply, in apoptosys our body would not want this effort to be done because the cells are dying. No need for further attention or fire-brigade services to keep them alive.

And I must start to think bio that doing lawns is a good preparation for biologists because you sited exactly the ONE sentence that supports that:

Phosphatidylserine inhibited the production of inflammatory mediators IL-6; IL-8; vascular endothelial growth factor [this is VEGF]; and, in particular, prostaglandin E(2) in IL-1ß-stimulated RA-FLS.

And that is WHY Gabrilovich is actively involved with PS-targetting/Bavituximab (and CD4/CD8+ helper cells levels and penetration in the tumour).

His VEGF approach COULD (as in not sure, not proven and PURE SPECULATION, but potentially possible and not far fetched) when combined with Bavituximab be a COMPLETE solution that does NOT NEED other combo drugs.


Some will say, hey that is not possible because what does replace the role that chemo/radio or IO drugs play in combo's and that makes Bavituximab work - namely cell damage with related PS-exposure?

The answer is VERY SIMPLE. With the described VEGF approach the affected vascular cells are actually KILLED, as with chemo/radio/IO; but by deprivation in this case and they ALSO start to expose PS more massively then in an apoptotic cycle. CELL-DEATH-->NO MORE FLIPASE->Phosphatidylserine (PS) Bi-Layer FLIPS inside out-->PS is exposed. And Bavituximab NEEDS that because if there is NO binding to PS then the Fc-Gamma binding CANNOT take place. Fc-Gamma binding with MDSC/M2 Macrophage receptors for Fc-Gamma is what activates the IL-12 and TGF-Alpha secretion that are the cytokines that STIMULATE the immune system (activate it) and make it possible for the auto-immune system that is activated with it the LEARN the condition and prevent RELAPSE.

Ofcourse if one can ALSO stop the CTLA-4 (T-Cell suppression) and PD-1 (programmed cell death), etc then the process may be sped up PROVIDED this doesn't MORE harm then good. Better a slow cure over several months with low or no side effects then a quick one that cures you and let side effects kill you.