Replies to post #132616 on Avid Bioservices Inc (CDMO)

[freethemice]

Yes, I have listened to the CC several times. I don't know what he means by an "upstream checkpoint inhibitor".
It is not at all that simple. What I think he means here is what Thorpe stated in the past, that is for bavi to be
able to mediate the destruction of the tumor vasculature the macrophages (TAMs) would have to be of the anti-tumor
M1 type. For that to be true, the tumor microenvironment must have been repolarized so that M2-like
macrophages became M1-like macrophages, and this is what bavi has done. This is where the thinking about
the MOA has changed since it is now recognized that the effect on the tumor vasculature is in reality a
manifestation of the change in the tumor microenvironment brought about by using bavi. As such there is
really no such thing as the "upstream checkpoint" since the tumor microenvironment is a very complicated
system of feedback loops between all the immune cells and the cytokines and chemokines which they produce
to influence each other. The "downstream checkpoint inhibitors" are the PD-L1 and PD-L2/PD-1 and the CD80
and CD86/CTLA-4 interactions between antigen presenting cells and activated T cells which are ways the
natural immune response to pathogens is controlled apart from the tumor microenvironment.