Replies to post #230443 on Avid Bioservices Inc (CDMO)

[2ndstr2thert]

And why do we want Docetaxel to ellicit PS ?

I got this from post 152368-Dr.Brekken's words-
" These are ( MDSC'S )-I have to describe them as teenagers. These are cells that have not developed into their final form...They are unproductive in a lot of ways.So MDSC'S are present in tumors and they have a phenotype that drives immunosupression. However because these are teenagers, you can educate( them ).You can drive them towards a productive endpoint...However, there are ways in which we can educate these MDSC'S to differentiate into cells that are productive with respect to generating an immune response."

[biopharm]

MDSCs reduced by more than 40% with PS Targeting so read the prior post and the following link and you will see why a big move up is coming

http://www.news-medical.net/news/20160902/Myeloid-derived-suppressor-cells-may-serve-as-biomarkers-for-idiopathic-pulmonary-fibrosis.aspx

[biopharm]

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.

...Dr. Jedd Wolchok also knows this and is why he is now coming out for PS Targeting in combo to help increase responders of other drugs.

A nice graph below, depicting just days after, how MDSC's increase and remember how clever Peregrine words things, like... "MDSC's were reduced by more than 40% .."

PS Targeting

PS Targeting

http://www.nature.com/articles/srep36663/figures/1

[biopharm]

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

Why ....some may ask and have asked and if you read the prior post it tells you ....and PS Targeting reduces MDSCs by at atleast 40%! ......now if we just have more out there saying that MDSCs are bad, then the potential for PS Targeting will become OBVIOUS! .....just in time.....London is calling

[quoteBreast cancer breakthrough: This technique could predict if disease will spread to lungs

BREAST cancer is the most common form of cancer affecting women. The disease is more deadly if it spreads, but now a new imaging technique could predict whether primary breast cancer will spread to the lung.

Wednesday August 16, 2017

Almost 54,000 new cases of breast cancer were diagnosed in the UK during 2013, according to Cancer Research UK figures.

In 2014, 11,400 people died from the disease.

Now scientists are hoping more lives could be saved following a medical breakthrough.

Scientists part-funded by Breast Cancer Now, the Medical Research Council (MRC) and other collaborators have developed an innovative imaging technique that could predict whether breast cancer will spread to the lung.

In a new study published in Theranostics, researchers have demonstrated in mice that a new non-invasive imaging method can be used to detect changes in the lungs that signal breast cancer may soon spread there – before any metastases are visible.

If given the green-light for use in humans, this approach could enable patients to be offered more intensive therapy earlier, to potentially prevent breast cancer spread.


Dr Fabian Flores-Borja, Research Fellow at the Breast Cancer Now Research Unit at King’s College London said: “By combining cell biology and imaging techniques, we have established a method to predict, at an early time-point during tumour development, whether tumour invasion will occur.

“We envision this technique being used to help select patients for either further surveillance or intensified therapy, as well as aiding cancer research.

“The development of a test that is able to identify an increased risk of metastasis soon after a patient is diagnosed with breast cancer, would be very useful in helping choose the best treatment for patients.”

Previous research has shown that the gathering of a special type of immune cell called ‘myeloid-derived suppressor cells’ (MDSCs) – in locations such as the lung – prepares the ground for breast cancer metastasis - spread.

This is because the local immune system is suppressed promotes the formation of new blood vessels - a condition called angiogenesis.

WHAT ARE THE SYMPTOMS OF BREAST CANCER?

Researchers at King’s College London have now developed a radioactive ‘tracer’ molecule to detect MDSCs accumulating in the lung in preparation for the arrival of breast cancer cells and the formation of metastases.

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, has hailed the news as ‘incredibly exciting’.

“While more research is needed before this could be tested in patients, the prospect of a hospital scan which could predict whether breast cancer will spread to the lungs is incredibly exciting.

“More immediately, this study brings a brand new method to the table that will help researchers unpick how the immune system is involved in the spread of breast cancer.

“Finding ways to predict and halt the spread of the disease will be crucial if we are to finally stop people dying from it.

“This is a promising step towards being able to use 3D imaging to help offer more personalised therapy. Ultimately, anything that could provide patients and their doctors with a more accurate picture of whether their breast cancer may spread will help us tailor treatments to stop this from happening.”

Dr Mariana Delfino-Machin, MRC Programme Manager for Cancer, said the research paves the way for new treatment in the clinic.

"Innovative, non-invasive imaging methods like this, which can help predict and diagnose disease as early as possible and avoid the discomfort of current invasive tests, have the potential to greatly impact cancer treatment and outcomes,” she said.

Experts said more studies are now required to develop a more effective ‘tracer’ molecule - suited for use in humans - to be tested in future clinical trials.


https://www.google.com/amp/s/www.express.co.uk/life-style/health/841398/breast-cancer-symptoms-spread-test-lung/amp
]

Flipped PS .......a perfect tracer molecule and why can't Peregrine BOD pick up an expert in MDSCs?? Oh yes....they did !

Dmitry Gabrilovich
the bottom line, Dmitry is the MD talking MDSC's and MDSC's "CAN" predict overall survival and he starts off the video with some general talking points re: leucocytes/neutrophils .. immune system..etc before showing in various cancer indications-- its MDSC's that speak the truth about overall survival.

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=104605941

______________

Who is putting this little puzzle piece together ?? Now we know why Dr Jedd Wolchok has said PS Targeting had no off target TOXICITIES .....so a great safety profile and I bet that has much to do with decreasing MDSCs !!

Why Ronin does not she'd some light on this is beyond me......so I don't trust any group who clearly is not seeing the potential in PS Targeting as many within Peregrine circles has shown, such as Dmitry Gabrilovich and Dr Jedd Wolchok has declared.

[biopharm]

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.

Lots of NEW info being learned in the MOA of PS Targeting as well as the MOA behind Halozyme IP assets that Helen Torley has found out....and seems like a perfect match as Helen may soon find out PS Targeting is required for the combo

2. MDSCs Generation and Expansion during Tumor Progression
Numerous reports published during the last decade described a strong correlation between the development of chronic inflammatory conditions in the tumor microenvironment and generation and expansion of MDSCs [1,2,3,4,18,23,24]. Furthermore, chronic inflammation has been found to be associated with the initiation and progression of various tumors [25]. Although the onset of some other tumors such as malignant melanoma is not generally associated with apparent inflammation, recent publications highlighted the critical importance of particular cytokines and chemokines for their fast progression [26]. Tumor cells are able to produce a variety of inflammatory mediators including granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF), vascular endothelial growth factor (VEGF), TGF-ß, tumor necrosis factor (TNF)-a, IL-1ß, IL-6, and IL-10 [1,2,3,4,26,27]. The effect of all these factors is combinatorial and dose-dependent. Furthermore, tumor cells can induce the production of these factors by fibroblasts and immune cells in the tumor stroma [1,28]. Moreover, stromal cells can further stimulate the production of inflammatory mediators by tumor cells thereby creating autocrine and paracrine loops in the tumor progression [29]. Altogether, these inflammatory factors can modulate myeloid cells in the tumor microenvironment, and having them delivered distantly to hematopoietic organs can change normal myelopoiesis and skew the differentiation of myeloid cells in favor of MDSCs
...
...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192356/#__ffn_sectitle

https://www.halozyme.com/investors/news-releases/news-release-details/2018/Halozyme-Publication-In-The-Journal-Clinical-Cancer-Research-Highlights-New-Nonclinical-Data-Supporting-Multiple-Effects-Of-PEGPH20-On-The-Tumor-Microenvironment/default.aspx

I wonder who is cross checking MOA of IP assets vs PS Targeting across Big Pharma