Replies to post #185480 on Avid Bioservices Inc (CDMO)

[biopharm]

MDSC's gone wild.... in Spain. Gotta love all this MDSC talk with the MOA of Bavi just sitting back and waiting for the right time.

Therese Liechtenstein1,2,
Noemi Perez-Janices1,3,
Maria Gato2,
Fabio Caliendo2,
Grazyna Kochan2,
Idoia Blanco-Luquin3,
Frederick Arce1,
David Guerrero-Setas3,
Joaquin Fernandez-Irigoyen4,
Enrique Santamaria4,
Karine Breckpot5,
David Escors1,2

1 Division of infection and immunity. Rayne Institute. 5 University Street. WC1E 6JF. London. UK.

2 Immunomodulation group. Navarrabiomed-FMS, calle Irunlarrea 3, 31008 Pamplona, Navarra, Spain.

3 Cancer Epigenetics group. Navarrabiomed-FMS, calle Irunlarrea 3, 31008 Pamplona, Navarra, Spain.

4 Proteomics Unit. Navarrabiomed-FMS, calle Irunlarrea 3, 31008 Pamplona, Navarra, Spain.

5 Laboratory of Molecular and Cellular Therapy. Department of Biomedical Sciences. Laarbeeklaan, 103/E, B-1090 Jette. Vrije Universiteit Brussel, Belgium.

Correspondence to:

Dr. David Escors, email: [e-mail]; [e-mail]

Received: June 29, 2014 Accepted: July 29, 2014 Published: August 4, 2014

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) exhibit potent immunosuppressive activities in cancer. MDSCs infiltrate tumors and strongly inhibit cancer-specific cytotoxic T cells. Their mechanism of differentiation and identification of MDSC-specific therapeutic targets are major areas of interest. We have devised a highly efficient and rapid method to produce very large numbers of melanoma-infiltrating MDSCs ex vivo without inducing tumors in mice. These MDSCs were used to study their differentiation, immunosuppressive activities and were compared to non-neoplastic counterparts and conventional dendritic cells using unbiased systems biology approaches. Differentially activated/deactivated pathways caused by cell type differences and by the melanoma tumor environment were identified. MDSCs increased the expression of trafficking receptors to sites of inflammation, endocytosis, changed lipid metabolism, and up-regulated detoxification pathways such as the expression of P450 reductase. These studies uncovered more than 60 potential novel therapeutic targets. As a proof of principle, we demonstrate that P450 reductase is the target of pro-drugs such as Paclitaxel, which depletes MDSCs following chemotherapy in animal models of melanoma and in human patients. Conversely, P450 reductase protects MDSCs against the cytotoxic actions of other chemotherapy drugs such as Irinotecan, which is ineffective for the treatment of melanoma.

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2279&path[]=3905

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MDSC's are spiking all over and completely setting up the PS Targeting introduction by Peregrine one of these days.

Sounds like a perfect time to release that publication Dr. Stopek and do I foresee some more MDSC talk out of University of Arizona ? Hopefully...

[biopharm]

This means oncologists do not want to be sticking needles in people for biopsies because it creates more inflammation and also because when one punctures tumors to see what they are cancer cells can be released out of their containment vessel (the tumor).

Biopsies have been around for years and who knows, in the years to come, maybe it will be possible to forego 90% of biopsies, as antibody/blood tests come online that will become sufficient.

There are about 1.5 Million liver biopsies completed earch year in the U.S. alone.

[biopharm]

Harold Dvorak : Peregrine Pharmaceuticals KOL : Cancer starts with Inflammation : Part II

...chronic inflammation fuels cancer.

The association between chronic inflammation and tumor development has long been known from the early work of German pathologist Rudolph Virchow. Harvard University pathologist Dr. Harold Dvorak later compared tumors with “wounds that never heal,” noting the similarities between normal inflammation processes that characterize wound healing and tumorigenesis or tumor formation.

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Harold Dvorak : 2014 Gairdner Lecture

“VPF/VEGF: Vascular permeability & pathological
angiogenesis in tumors, wounds & chronic inflammation”

Thursday, October 23, 2014
12 noon - 1:00 p.m.
Frederic Gaspard Theatre
Basic Medical Science Building
Bannatyne Campus

YOU AND A GUEST TO THE
Thursday, October 23, 2014
12 noon - 1:00 p.m.
Frederic Gaspard Theatre
Basic Medical Science Building
Bannatyne Campus
GAIRDNER LECTURE
PRESENTED BY HAROLD F. DVORAK MD
Mallinckrodt Distinguished Professor of Pathology, Harvard Medical School
Director, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Recipient: Canada Gairdner International Award, 2014
2014

In 1983, Dr. Dvorak and his colleagues were the first to demonstrate that tumor cells secreted vascular
endothelial growth factor (VEGF), known at the time as vascular permeability factor or VPF. This seminal
discovery provided the molecular basis for the field of angiogenesis. Dr. Dvorak went on to make the
critically important observation that tumors behave like “wounds that do not heal” in that the vascular and
stromal responses they induce closely mimic those of healing wounds. More recently, his work has
characterized the different types of blood vessels that tumors generate and the molecular mechanisms by
which they form.

Dr. Dvorak has taught for many years at the Harvard Medical School, and has lectured frequently as a
visiting professor and at numerous national and international scientific conferences. He is a fellow of the
American Association for the Advancement of Science and of the National Foundation for Cancer Research
and has served as President of the American Society for Investigative Pathology which awarded him the
2002 Rous-Whipple award the Gold-headed cane award for his scientific accomplishments. In 2005 he
received the Grand Prix Lefoulon-Delalande from the Institut de France and in 2006 the inaugural Albert
Szent-Gyorgyi Prize for Progress in Cancer Research from the National Foundation for Cancer Research (NFCR).

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Collegiate students to take in lecture from renowned cancer researcher

Oct 20, 2014

Dr. Harold Dvorak will deliver his student lecture "What does cancer have to do with a cut finger?" on Thursday, October 23, at 2:30 pm.

http://www.noodls.com/view/4D1B622A3E08829B10236B733BA2293344DDA8E1?5529xxx1413835002


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October 30, 2014

9:40 am–10:10am (30 mins)
VPF/VEGF: Vascular permeability & pathological angiogenesis in tumors, wounds & chronic inflammation
Dr.Harold Dvorak 2014 Canada Gairdner International Laureate,
Beth Israel Deaconess Medical Center, Boston,
MA, USA

1:05 am-1:35pm(30 mins)
Targeting immune checkpoints in cancer therapy
Dr. James Allison 2014 Canada Gairdner International Laureate,
University of Texas, Houston, USA

http://www.gairdner.org/sites/default/files/downloads/2014_canada_gairdner_recipients_lecture_october_30_2014pdf.pdf

http://www.gairdner.org/content/about-our-events

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