Replies to post #147369 on Biotech Values

[Robert C Jonson]

I'm not really sure how this provides a means for the cell to "escape" apoptosis. PS is flipped to the outer leaflet during apoptosis, at which point it is recognized by phagocytes directly (see ref). So if a cancer cell is exposing PS on the outer leaflet, it is doing the exact opposite of disguising itself... it is in fact putting out a very specific signal for phagocytes to come and engulf it. So the disguise angle makes little sense. If anything, the antibody binding the phosphatidylserine would help disguise the cell from the phagocytes.


PGS, it looks like only apoptotic cells activate the phagocytes according to Dr. Thorpe. In the non-apoptotic cancer cells, the exposed PS serves only to disguise them from an immune reaction:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071078/

The expression of PS at the cell surface inhibits immune responsiveness and, in the case of apoptotic cells, also serves as a recognition ligand and binding site for phagocytes [4,5].

[exwannabe]

I would also expect that if this anti-PS antibody was really working, you'd expect bleeding as a mechanistic side effect in patients. Activated platelets expose phosphatidylserine to accelerate clotting (see ref). If anything, the antibody would inhibit this acceleration and decrease the efficiency of clotting.

So will we soon see a trial for Bavi for prevention of clots post hip replacement surgery?

[vinmantoo]

<<Quote:
this immune response may be requiring a bit of time...that's where the 'slower' comment comes from>>

Poorgradstudent responds with

{{For the immune system, passive memory is evident within days. Active memory is evident within weeks, with IgGs developing within 2 months.

That's not slow given the median survival numbers that are talked about. The "slow" explanation is often invoked for cancer immunotherapies, largely by companies that have immunotherapies that don't elicit effective immune responses.}}


Thanks. You are right on the mark. I thought I was missing something as Bavi is an antibody not an immune training based therapy or an induced immune response based therapy. This whole idea of slow responses is absolute BS. Once the Bavi antibody binds to exposed PS, it would stimulate ADCC and or the complement pathway without any delay, or certainly a "delay" no different than any other antibody anti-cancer therapy .

[cjgaddy]

Poorgrad, if you have the time & desire, listen to the replays of these 5 researchers at the 5-1-12 NYAS “Phosphatidylserine (PS) Asymmetry - Therapeutic Applications in Cancer & Infectious Disease Symposium in NYC. Of the 5, prioritize to Dr. Alan Schroit (MDA/UTSW - the master of cellular membrane expression) and Dr. Phillip Thorpe (UTSW - the inventor of PS-targeting therapeutics, including Peregrine’s Bavituximab).

They’re all good, but the Thorpe & Schroit talks will cram your brain full and answer all your questions about "PS exposure, its biological consequences, and its exploitation to create novel agents for the detection and treatment of cancer & viral diseases", I think.

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