Avid Bioservices Inc (CDMO)

[biopharm]

CTC's > back to extracting CTC from the blood... analyze... treat cancer like diabetes....

Ok... homework assignment for next week: CTC's vs MDSC's and since Peregrine KOL Dmitry Gabrilovich is on board backing MDSC's, lets see if we are competing against CTC's or ?? So from 2009 till 2014... the smart few have seen the light and it shows MDSC's just may be that surrogate endpoint that many are waiting for, because if they are statistically significant enough to detect you have cancer.... the FDA can just as easily allow them to decide and predict survival outcome.

Blood based biomarkers are here and now it should be clear to see why Peregrine has set a path to scientifically prove that PS Targeting decreases MDSC's through their Key Opinion Leaders and extended global network.

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2009

Elevated Circulating Myeloid Derived Suppressor Cells (MDSC) Are Associated with Inferior Overall Survival (OS) and Correlate with Circulating Tumor Cells (CTC) in Patients with Metastatic Breast Cancer.

Using a generalized estimating equation regression model the percentage of MDSC in peripheral blood was found to have a close correlation with CTC (Pearson correlation 0.62, p=0.0001) and a coefficient of 0.29 (0.14, 0.43 95%CI). The correlation between percent MDSC and SS was not significant (Pearson 0.31, p=0.12). Interestingly, no significant correlation between CTC and SS was noted either. MDSC levels were also found to predict OS in patients with the highest percentages at the first visit having significantly decreased median overall survival [6.8 vs. 19.6 months; p=0.05]

http://cancerres.aacrjournals.org/content/69/24_Supplement/4135.short

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2014

The role of myeloid-derived suppressor cells in immune ontogeny

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of granulocytic or monocytic cells that suppress innate as well as adaptive immune responses. In healthy adults, immature myeloid cells differentiate into macrophages, dendritic cells, and granulocytes in the bone marrow and MDSC are rarely detected in peripheral blood. However, in certain pathologies, in particular malignancies and chronic infection, differentiation of these cells is altered resulting in accumulation of circulating suppressive myeloid cells. MDSC express suppressive factors such as arginase-1, reactive oxygen species, and inducible nitric oxide synthase, which have the ability to inhibit T cell proliferation and cytoxicity, induce the expansion of regulatory T cells, and block natural killer cell activation. It is increasingly recognized that MDSC alter the immune response to several cancers, and perhaps chronic viral infections, in clinically important ways. In this review, we outline the potential contribution of MDSC to the generation of feto-maternal tolerance and to the ineffective immune responses to many infections and vaccines observed in early post-natal life. Granulocytic MDSC are present in large numbers in pregnant women and in cord blood, and wane rapidly during infancy. Furthermore, cord blood MDSC suppress in vitro T cell and NK responses, suggesting that they may play a significant role in human immune ontogeny. However, there are currently no data that demonstrate in vivo effects of MDSC on feto-maternal tolerance or immune ontogeny. Studies are ongoing to evaluate the functional importance of MDSC, including their effects on control of infection and response to vaccination in infancy. Importantly, several pharmacologic interventions have the potential to reverse MDSC function. Understanding the role of MDSC in infant ontogeny and their mechanisms of action could lead to interventions that reduce mortality due to early-life infections.

Affiliation
Seattle BioMed , Seattle, WA , USA ; Janssen ID&V Research and Development , Antwerp , Belgium.

http://www.pubfacts.com/detail/25165466/The-role-of-myeloid-derived-suppressor-cells-in-immune-ontogeny.

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Interesting to see Janssen up there (Veridex is part of them now) and did they back CTC's and/or MDSC's ? To show the power of blood based biomarkers, whether MDSC or CTC's..etc, pay attention to the link below and the footnote below. Blood based biomarkers that will most probably detect cancer many months before it would normally have been detected? I say yes

"One patient in the benign group has as high as 12 CTCs and was later found to have MBC about 6 months later"

https://www.cellsearchctc.com/significance-ctcs

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For those that are trying to figure out what this has to do with Peregrine... well its simple.

1) MDSC's are just as effective or better than CTC's
2) Peregrine KOL's such as Dmitry Gabrilovich has spent his career in understanding MDSC's and KOL David Carbone is soon to be President of IASLC and he backs blood based biomarkers as well.
3) We must not forget Peregrine, since they have this patent on PS Targeting and Bavituximab has been proven to decrease MDSC's

I think the puzzle is shaping up nicely and I'm sure I'm missing dozens of other supporting facts, but I'm Turkey tired.