Avid Bioservices Inc (CDMO)

[freethemice]

If you want to do some reading the paper you cite is freely available to anyone
http://www.neoplasia.com/abstract.php?msid=5083

The "inflammatory intratumoral infiltrates" in this case are neutrophils and macrophages. Both
were mostly in the N1 and M1 state which are immunostimulatory and are able to phagocytose the tumor
vasculature cells opsonized with bavi. The neutrophils, which are granulocytes, are involved probably
because in this case surgery was done first, and then bavi and cisplatin given. The effect of surgery
is like a response to a wound when neutrophils quickly arrive at the scene. These cells are described as
inflammatory because of the types of cytokines they release. In Thorpe's NYAS webtalk he talks of these.
The whole idea of switching the macrophages from a pro-tumor M2 state to a anti-tumor M1 state lies
at the heart of understanding the MOA. If this does not occur then the macrophages won't
be able to phagocytose the tumor vasculature endothelial cells which have PS exposed on them.
So bavi first has to enable this switch by a process Thorpe talks about in the NYAS talk and I have
diagrammed here

So the tumor microenvironment is switched from a immunosuppresive state to a immunostimulatory state.
Then the arriving neutrophils which enter the tumor remain in their N1 state and are not switched to a N2 state.
It is thought that the presence of the cytokine TGF-beta does this. When the tumor microenvironment
is in the immunosuppressive state TGB-beta is produced by the macrophages, but when the macrophages
are switched to the M1 state by bavi then TGF-beta is not produced. The concept of how the immune cells
behave, either pro- or anti-tumor, depending on the local conditions in and around the tumor site, i.e. what
cytokines are present, is crucial to understanding how bavi works.