Avid Bioservices Inc (CDMO)

[biopharm]

MDSC; the Most Important Cell You Have Never Heard Of

R.J. Tesi
Published:December 06, 2018

The myeloid-derived suppressor cell (MDSC) is the ‘queen bee’ of the tumor microenvironment. MDSCs protect the cancer from the patient’s immune system, make the tumor resistant to immunotherapy, and allow the tumor to thrive while the patient withers away. Eliminating MDSCs should improve response rates to cancer therapy and patient survival.

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(18)30189-5

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John Springs Stafford lied to Peregrine Pharmaceuticals shareholders in some comments and some will stop at nothing to try and have control of the IP because PS Targeting has been proven to be the most upstream FIRST order of event that needs to take place to give any BP IO drug a chance at holding an FDA approval

"such as myeloid-derived suppressor cells (MDSCs), were reduced by more than 40% in the combination with the PS-targeting antibody versus anti-PD-1 alone."

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Sunday, 08/16/15 04:50:50 PM

Re: 2ndstr2thert post# 230440 0
Post # of 330465

"I do not understand why reducing MDSC'S is a good thing."


I'd read over one of the key Peregrine Pharmaceuticals press releases, where they specifically mention that PS Targeting allows for the reduction by at least ==> because they cleverly said "more than : ) "<== 40% to MDSC's and that is a good thing. Actually, I've said it before in a post or two or more... that "NO OTHER" biotech has ever disclosed that the result of the MOA of any immunotherapy agent was capable of reducing MDSC's by as much as 40%. Now, we must ask more question.... would this large reduction in the area of MDSC's be part of much of the reason why PS Targeting combinations with PD-1/PD-L1..etc..etc allows for a statistically significant percent increase in ORR of 200-300% than without PS Targeting in the mix ? I say yes

I'd read this PR over again and look how Opdivo/Nivolumab/Keytruda..etc..etc makes mention that their drug "INTERACTS" with MDSC's and they never disclose how exactly they interact ?? lol Does Opdivo/Nivolumab/Keytruda..etc..etc and all others reduce MDSC's by 5% or up to at least 40% as Peregrine has revealed. My guess is those other IO drugs do not have anything close to the effect to restore and bring about optimal immune responses as PS Targeting (Bavituximab) does and that is why only Peregrine mentions the 40% reduction number in MDSC's. Next, are they going to be conservative with that percentage ? : ) I say yes...again. Always save the best for when you think you are given the best deal possible by some Big Pharma, then you bring out the best of the best facts that warrants the biggest biotech buyout of all time. Period.... and notice no question marks : ) No exclamation marks neither because one must remain calm at the bargaining table when one knows they have everything all other parties want and to the degree that illegal sabotage attempts/acts would be chosen by some as well.

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Quote:
February 9, 2015

Newly Presented Data Shows That Peregrine Pharmaceuticals' PS-Targeting Antibodies Significantly Enhance Anti-Tumor Activity of Immune Checkpoint Inhibitors PD-1 and CTLA-4 in Models of Breast Cancer and Melanoma

PS-Targeting Antibodies Block Tumor Suppression of Immune System Allowing Development of Robust Immune Responses Resulting in Statistically Significant Improvement in Anti-Tumor Activity; Specific Effects Seen in Decreased Levels of MDSCs and Other Immunosuppressive Lymphocytes and Increases in Tumor Fighting Immune Cells

TUSTIN, CA -- (Marketwired) -- 02/09/15 -- Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) (NASDAQ: PPHMP) today announced preclinical data presentations showing that the PS-targeting antibody equivalent to bavituximab combined with an anti-PD-1 antibody displayed statistically significant improvement in tumor fighting immune cells, activation signals and cytokines in a model of melanoma compared to anti-PD-1 alone. Moreover, cells that suppress the immune system from recognizing tumors, such as myeloid-derived suppressor cells (MDSCs), were reduced by more than 40% in the combination with the PS-targeting antibody versus anti-PD-1 alone. These data, further validating the immune-stimulatory mechanism of bavituximab, are outlined in an oral and poster presentation by Bruce Freimark, Ph.D., director, preclinical oncology research at Peregrine, to be made at the Keystone Tumor Immunology: Multidisciplinary Science Driving Combination Therapy meeting being held February 8-13, 2015 in Banff, Alberta, Canada. Peregrine's lead PS-targeting antibody, bavituximab, is currently being evaluated in second-line non-small cell lung cancer (NSCLC) as part of the SUNRISE pivotal Phase III clinical trial.

"These data build on our growing body of encouraging combination data and strengthen our clinical development plans as we evaluate the direction of combination therapy trials utilizing bavituximab and other checkpoint inhibitors" said Jeff T. Hutchins, Ph.D., vice president of preclinical research at Peregrine. "Our goals are to modify a tumor environment that allows more patients to respond to conventional and immune therapy. As the tumor environment switches from immuno-suppressive to immuno-stimulatory with bavituximab treatment, we believe the addition of other checkpoint inhibitors, like anti-PD-1, may increase the number of patients responding to therapy."

In the presentations titled: "Antibody-Mediated Blockade of Phosphatidylserine Enhances the Anti-Tumor Activity of Immune Checkpoint Inhibitors by Affecting Myeloid-Derived Suppressor Cells (MDSC) and Lymphocyte Populations in the Tumor Microenvironment", Dr. Freimark and his research group, along with colleagues from the University of Texas Southwestern Medical Center led by Xianming Huang, Ph.D., demonstrate that in immunocompetent preclinical models of breast cancer and melanoma, the combination of PS-targeting antibodies and anti-CTLA-4 and anti-PD1 antibodies demonstrate statistically significant anti-tumor responses than either anti-CTLA-4 or anti-PD-1 antibody alone. New data presented show statistically significant changes in levels of tumor infiltrating lymphocytes (TILs), a type of white blood cell implicated in killing tumor cells, in the PS-targeting and anti-PD-1 combination group over single treatment alone in a melanoma model. Specifically, data show increases in a number of markers used to determine immune activation, including CD3 and CD8 cells expressing PD-1, Lag-3 and CD137 (4-1BB). Furthermore, data show that CD8 T cells in the tumor had increased production of IFN-gamma and TNF-a, both known to assist in promoting immune activation and Granzyme-B which is involved in direct tumor killing.

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=895363