Replies to post #146960 on Biotech Values

[dia76ca]

You may also want to consider this interesting information in a post on the PPHM board from freethe mice to RRdog.


freethemice
Monday, August 06, 2012 11:58:38 PM
Re: RRdog post# 85801
Post # of 86420

RRdog, the fact that neutrophils are involved with the response to bavi is indeed new and exciting.
The fact that neutrophils can be polarized to an N1 and N2 phenotype, much as macrophages are
polarized to M1 and M2 phenotypes, has been known for a few years. However, this is the first time
it has been shown that these N1 neutrophils can be induced to attack a tumor, as far as I know. I believe
that what is happening is that bavi is altering the tumor microenvironment by masking PS and by
directly switching macrophages from M2 to M1. When neutrophils are recruited to the tumor they then
remain in the N1 state instead of being switched to the tumorgenic N2 state, as they would be if bavi wasn't used.

The paper is here http://www.ncbi.nlm.nih.gov/pubmed/22577350

Vascular endothelial-targeted therapy combined with cytotoxic chemotherapy induces inflammatory
intratumoral infiltrates and inhibits tumor relapses after surgery.
Judy BF, Aliperti LA, Predina JD, Levine D, Kapoor V, Thorpe PE, Albelda SM, Singhal S.

Discussion
The objective of this study was to determine whether using targeted
vascular therapy after surgery could inhibit local tumor recurrences
without causing the toxicity associated with other vascular-targeting
agents. Our major finding from this study is that combining mch1N11
with cis slows tumor recurrences after surgery. Our data suggest that the
mechanism is that cis, either directly or indirectly (i.e., by killing tumor
cells that then activates their associated vasculature), increases PS expression
of the tumor vasculature. This vascular PS presents a target
for the mch1N11 antibody that binds and induces intense neutrophil
infiltration, leading to vascular disruption and tumor death. This
process seems independent of the adaptive immune system.
....
Note that mch1N11 is the mouse chimeric version of PGN635, and cis is csiplatin. Also,
they show in the paper that macrophages are being switched from M2 to M1, in fact there are
twice as many M1 as M2 macrophages after treatment with bavi, in addition to the neutrophils.