Replies to post #274871 on Avid Bioservices Inc (CDMO)

[biopharm]

What are the most promising potential strategies for targeting MDSCs in cancer therapy?
There are number of ways to target MDSCs. Direct elimination with a specific antibody would be the preferable way, but clinical data are not yet available. Chemotherapeutics like gemcitabine and others can kill MDSCs, but obviously their specificity is very limited. The other ways to target MDSCs include to differentiate these cells or inhibit their production. All-trans retinoic acid was shown to have some effect, and histone deacetylase inhibitors are promising.

A number of other strategies are currently being tested; MDSCs can be also targeted by inhibiting their ability to suppress immune responses. This includes using drugs such as sildenafil, triterpenoids, inhibitors of COX-2, inducible nitric oxide, etc. Migration of MDSCs to the tumor site can be blocked by targeting chemokine receptors, like CXCR2, as well as some chemokines, like IL-8.

Time to pick things apart little by little.... lets just take COX-2

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Prostaglandin E Receptor EP4 expression, survival and pattern of recurrence in locally advanced NSCLC

Neha Bhooshan, M.D., Ph.D.
Paul N. Staats, M.D.
Amy M. Fulton, Ph.D.
Josephine L. Feliciano, M.D.
Martin J. Edelman, M.D.

Abstract
Background

Elevated COX-2 expression has been correlated with inferior outcome in NSCLC. COX-2 catalyzes the transformation of arachidonate to PGE2. We and others have demonstrated that PGE2 induces proliferation and metastatic spread and immunosuppression through the G protein-coupled EP4 receptor. We hypothesized that EP4 expression on malignant cells would correlate with outcome and patterns of relapse after treatment of LANSCLC stage IIIA (7th edition, N2+).
Methods

Tissue specimens from 41 pts treated for LANSC at UMGCC were obtained. A tissue microarray was prepared and examined for EP4 expression. Intensity of staining was scored semi-quantitatively as 0–4 in both the nuclear and cytoplasmic compartments by a pathologist blinded to the clinical data.
Results

EP4 nuclear staining 0–1 vs. 2+ was associated with overall survival, (OS) (44.3 vs. 18 mo; HR = 0.41, p = 0.024) and numerically superior progression free survival (PFS) (16.4 vs. 10.2 mo, p =0.16). EP4 cytoplasmic staining did not correlate with OS (0–1 vs. 2+, 23.8 vs. 28.8 mo; HR = 1.2, p = 0.81). Relapse pattern (no relapse or local vs. systemic) did not correlate with EP nuclear staining (p = 1.0, X2).
Conclusions

This is the first clinical study of EP4 expression in lung cancer. There was a significant correlation between OS and nuclear EP4 expression, indicating that this is a potential therapeutic target. Studies with AT-007, a specific inhibitor of EP4, are planned to commence this year.

www.lungcancerjournal.info/article/S0169-5002(16)30477-9/abstract

You think Dr. Edelman just decided out of the blue to concentrate on COX-2...or maybe it was his way to eventually work with PS Targeting in a timely manner and help out...? hmmm and this ties in nicely to pre-market Monday morning news re: biomarkers and Peregrine and how?? well just take a look at this link below, read slowly all the authors associated and you land on Dr. David Spigel, the presenting/lead author Monday : )

Looking at Dr. Martin Edelman for now...but first everyone should know, if one did not truly know... that Dr. Martin Edelman was a Bavituximab supporter and not saying he is not no longer, but we will soon find out.

Dr. Martin Edelman: "I look forward to being involved in the upcoming Phase III trial and to seeing the potential of bavituximab in other indications and combinations," said Martin J. Edelman, M.D., Professor of Medicine at the University of Maryland Greenebaum Cancer Center

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=106609477

...and if you have been paying attention, of course you know David was promoted to CSO Chief Scientific Officer at Sarah Cannon Research Institute this year and can you imagine that ?

David working with Peregrine and PS Targeting and now, all of a sudden promoted to CSO ! A coincidence ? I think not. Nice to see BI Boehringer Ingelheim teaming up with SCRI now as well...

The largest puzzle one will ever try to piece together and are we ready for the climb back to $5.40 again? I say yes

.... now tomorrows job is to check AT-007 and is it this...?

lead product candidates, AT-001, AT-002, AT-003, AT-004, AT-005, AT-006 , AT-007, AT-008 and AT-014

http://www.prnewswire.com/news-releases/aratana-therapeutics-presents-safety-and-clinical-findings-at-2014-acvim-forum-262361981.html

Is someone letting the dogs out?
http://www.aratana.com/pipeline/