Avid Bioservices Inc (CDMO)

[biopharm]

BioBS2012, I have found so many links on MDSC's <> Notch Signaling that I believe the powers to be are still trying to figure out how they will write the text book so to speak on what cascade of events that occur.... would be considered part of those cascade of events that are typically called Notch Signaling. Basically... would MDSC changes be considered part of Notch Signaling or just a result of what happens due to Notch Signaling? Either way, targeting flipped PS that exists on all cancers, exists on hundreds of auto-immune diseases, blood diseases..etc..etc..etc shows the rise of flipped PS and this results are now being found to also show a rise in MDSC's.

I've posted many of Dmitry Gabrilovich work on MDSC's and here is just one of them that ties it into Notch Signaling:

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Effects of notch signaling on regulation of myeloid cell differentiation in cancer.

2014

Cheng P1,
Kumar V,
Liu H,
Youn JI,
Fishman M,
Sherman S,
Gabrilovich D.

Author information

1Authors' Affiliations: H. Lee Moffitt Cancer Center, Tampa, Florida; The Wistar Institute, Philadelphia, Pennsylvania; and University of Nebraska Medical Center, Omaha, Nebraska.

Abstract

Functionally altered myeloid cells play an important role in immune suppression in cancer, in angiogenesis, and in tumor cells' invasion and metastases. Here, we report that inhibition of Notch signaling in hematopoietic progenitor cells (HPC), myeloid-derived suppressor cells (MDSC), and dendritic cells is directly involved in abnormal myeloid cell differentiation in cancer. Inhibition of Notch signaling was caused by the disruption of the interaction between Notch receptor and transcriptional repressor CSL, which is normally required for efficient transcription of target genes. This disruption was the result of serine phosphorylation of Notch. We demonstrated that increased activity of casein kinase 2 (CK2) observed in HPC and in MDSC could be responsible for the phosphorylation of Notch and downregulation of Notch signaling. Inhibition of CK2 by siRNA or by pharmacological inhibitor restored Notch signaling in myeloid cells and substantially improved their differentiation, both in vitro and in vivo. This study demonstrates a novel mechanism regulation of Notch signaling in cancer. This may suggest a new perspective for pharmacological regulation of differentiation of myeloid cells in cancer.

http://www.ncbi.nlm.nih.gov/pubmed/24220241

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Now... I think this is why our KOL's were chosen so carefully. Dmitry is the MD of MDSC's and actually coined the term MDSC's and he has spent his lifes work on researching Myeloid Derived Suppressor Cells and my last post where I seen David Carbone showing up at a "Notch .. conference" back in 2008 in Greece and Dmitry showing up at the world Notch Conference just this past summer... it just becomes clear that Peregrine can't just say Bavi and PS Targeting works, but more importantly why it works. By digging deeper and knowing more about Notch and why a drug works.... well, it looks like they can also start telling why a drug doesn't work and interesting this Roche drug = Erlotinib is said (by Peregrine KOL David Carbone that "dual targeting" may be needed. This seems to hopefully be setting up PS Targeting as that much needed and required target in order to improve Erlotinib and improve just about all over medicines. I think when this was found out way back when.... thats when the goal was not to work with one Big Pharma but get Bavi in the hands of many ( dozens of collaborations ..) and that way, its highly unlikely that one Big Pharma will pay off all other Big Pharmas lol or better yet, all we need is one Big Pharma to seize the opportunity and I believe that one Big Pharma is ready to piggy back along with PS Targeting and stay in business for another hundred years.


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Now, what is important ( in my opinion ) is that Big Pharma just may realize that allowing Bavi to be combined with everything and let current SOC keepers, maintain their SOC's eventually vs allowing Peregrine the (possible) opportunity to actually start dismissing drugs that do not work based on Notch Signaling events.

Time will tell.... but Notch Signaling is certainly on every ones radar and since PS Targeting reduces MDSC's and MDSC's are directly/indirectly related to Notch Signaling, how long will this take to play out before Peregrine reaches $100 per share? I do believe that Peregrine is playing nice because they could just start announcing all this now, but it seems to be playing out slowly for some Big Pharma reason.

Its just a matter of time

The researchers found that when erlotinib blocks EGFR, it activates a second signaling molecule called Notch3. Activation of that pathway leads to increased development of cancer stem cells among the surviving tumor cells and to accelerated tumor growth.

"Our findings might explain why erlotinib in clinical trials seems to worsen survival in patients with early-stage lung cancer," says co-corresponding author David Carbone, MD, PhD, professor of medicine, Division of Medical Oncology at the OSUCCC -- James. "They also suggest that combining an EGFR inhibitor with a Notch inhibitor should overcome the effect."


"We found that the activated, mutated EGFR directly inhibits Notch signaling, and that inhibiting EGFR with erlotinib removes this restraint and activates Notch signaling," says Carbone, who is the Barbara J. Bonner Chair in Lung Cancer Research. "It suggests that specific dual targeting might overcome this adverse effect."

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=107705011&txt2find=david|carbone