Replies to post #191497 on Avid Bioservices Inc (CDMO)

[biopharm]

Hakan Mellstedt : Peregrine Pharmaceuticals KOL :

I try to place any news related to the MOA of Bavi/PS Targeting from each of the 4 KOL's added Dec 10, 2013 (Dmitry Gabrilovich, David Carbone, Scott Antonia and Hakan Mellstedt) under each one.... and since I've already mentioned the book below authored by Dmitry, it does related directly over to Hakan Mellstedt and his research at Karolinska. Again, each KOL was strategically chosen and all will benefit by sort of being the latest of the chosen ones to have complete, up to date knowledge of why PS Targeting will be not just important... but simply vital for any immunotherapy to truly be called immunotherapy at all.

---------------------------------

1) Tumor-Induced Immune Suppression - Prospects and Progress in Mechanisms and Therapeutic Reversal

Author - Dmitry Gabrilovich 2nd Edition 2014

http://www.freshwap.me/5882240-tumor-induced-immune-suppression-mechanisms-and.html

-------------------------------------------------------------

2) We've seen these terms used many times: "Tumor-Induced Immune Suppression" and lets recall back in April of 2010 at AACR

New Preclinical Breast Cancer Study Shows Peregrine's PS-Targeting Antibodies Can Reverse Tumor-Induced Immune Suppression

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=461029

-------------------------------------------------------------

3) Now..again, these words are at the core of "Immunotherapy"... and lets start to connect them to Karolinska and Hakan Mellstedt

Tumour-induced immune suppression: role of inflammatory mediators released by myelomonocytic cells

March 24, 2014 (yes... March Madness 2014)

Y. Mao1,
I. Poschke2 and
R. Kiessling1,*

Author Information

1 Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
2 German Cancer Research Center (DKFZ), Heidelberg, Germany

Abstract

Tumour-induced immune dysfunction is a serious challenge to immunotherapy for cancer, and intact adaptive and innate cellular immunity is key to its success. Myelomonocytic cells have a central role in this immune suppression, and tumour-associated macrophages, eosinophils, neutrophils and myeloid-derived suppressor cells have all been shown to be of major importance. These myelomonocytic cells secrete a broad repertoire of inflammatory mediators providing them with powerful tools to inhibit tumour-reactive T cells and natural killer cells; free oxygen radicals including reactive oxygen species and NO, arginase, indoleamine 2,3-dioxygenase, prostaglandins, the pro-inflammatory heterodimer S100A8/9 and cytokines, such as granulocyte–macrophage colony-stimulating factor and transforming growth factor-ß, have proven particularly potent in suppressing antitumour cellular immunity. Determining which of these factors prevail in individual cancer patients and designing methods aimed at neutralization or inhibition of their effects on target tissues have the potential to greatly enhance the clinical efficacy of immunotherapy.

http://onlinelibrary.wiley.com/doi/10.1111/joim.12229/abstract

------------------------------------------------------

4) Rolf Kiessling's Group

Members and group leaders in IMTAC are;


Håkan Mellstedt, Cancercenter Karolinska, Karolinska Institutet.

Ola Winqvist, Department of Medicine, Karolinska Institutet

Klas Kärre, Microbiology and Tumor Biology Center, Karolinska Institutet

Kalle Malmberg, Department of Medicine, Karolinska Institutet

Annika Scheynius, Department of Medicine, Karolinska Institutet.

Petter Höglund, Microbiology and Tumor Biology Center, Karolinska Institutet


Additional examples of collaborators at Karolinska Institutet


Giuseppe Masucci, Cancer Centrum Karolinska, Karolinska Institutet

Johan Hansson, Cancer Centrum Karolinska, Karolinska Institutet

Katarina Le Blanc, Clinical Immunology, Karolinska Institutet

Kalle Malmberg, Centre of Infectious Medicine, Karolinska Institutet

Lars Holmgren, Cancer Centrum Karolinska, Karolinska Insitutet

Olle Larsson, Cancer Centrum Karolinska, Karolinska Institutet

Stefan Seregard, St. Erik Eye Hospital, Karolinska Institutet

Tina Dalianis, Cancer Centrum Karolinska, Karolinska Insitutet


External collaborators


Andrew Quest, University of Chile, Santiago, Chile

Barbara Seliger, Martin-Luther University, Halle-Wittenberg, Germany

Brahm H. Segal, Roswell Park Cancer Institute, University of Buffalo, USA

Federica Cavallo, University of Turin, Italy

Flavio Salazar-Onfray, University of Chile, Santiago, Chile

Göran Stenman, University of Gothenburg, Sweden

Guido Forni, University of Turin, Italy

Jehad Charo, Max-Delbruck Center for Molecular Medicine Berlin, Germany

Koji Kono, Yamanashi Medical University, Yamanashi, Japan

Kousako Mimura, Yamanashi Medical University, Yamanashi, Japan

Michael I. Nishimura, Medical University of South Carolina, USA

Takashi Ando, Yamanashi Medical University, Yamanashi, Japan

Wei-Zen Wei, Karmanos Cancer Center, Wayne State University, USA


Collaborators in Industry

BioInvent International AB, Sweden
Cyto-Pulse Science, Inc, Stockholm, Sweden
Mabtech AB, Nacka, Sweden
Philochem AG, Switzerland
Protagen AG, Dortmund, Germany
ThromboGenics NV, Belgium


-------------------------------------------------

http://www.researchgate.net/profile/Isabel_Poschke



Isabel Poschke
Rolf Kiessling

ABSTRACT Myeloid-derived suppressor cells (MDSC) have frequently been observed in patients with cancer. This heterogeneous population of myeloid cells can exert potent suppression of lymphocyte function and thereby poses a significant hurdle to natural or therapeutically induced anti-tumor immunity. On the other hand, the natural function of MDSC is not yet well understood and their role in infection, inflammation and autoimmune disease is still puzzling. Understanding MDSC biology will provide the tools necessary for therapeutic targeting of this population, but also permit exploitation of their strong tolerogenic function in the treatment of inflammatory conditions and the prevention of graft rejection.

http://www.researchgate.net/publication/230615237_On_the_armament_and_appearances_of_human_myeloid-derived_suppressor_cells

-------------------------------------------------------

There are still, even more puzzle pieces that off shoot from all these above leading into/out of Karolinska, but one thing is for sure: MDSC's and the Notch Signaling pathway and all those cascade of events that take place ( that I've mostly placed under KOL Dmitry Gabrilovich's link of posts ) are all parts of the sum that explain why/how the MOA of Bavituximab and one day, hopefully soon... Peregrine is allowed to tell all. We certainly will not be a sub $2 stock at that time.

[biopharm]

Peregrine Pharmaceuticals : KOL Hakan Mellstedt

Ok.... digging deeper, we have Advisor: Dr. Mahmoud Jeddi-Tehrani, tied directly into Peregrine KOL Hakan Mellstedt:
If you look at the publications... Hakan Mellstedt is all over the place with Dr Mahmoud Jeddi-Tehrani, and Dr. Jeddi-Tehrani has roots back in Karolinska, home of Hakan Mellstedt

.... just a little clip from one of the many chain of posts re: Hakan Mellstedt and to continue on and see how he is playing into this Peregrine puzzle and how it will unfold. First to show the top co-authors again of Hakan M:

---------------------------

Hakan Mellstedt:

Top Co-authors View all

Jan-Erik Frodin (58)
Karolinska Institutet

Peter Ragnhammar (41)
Karolinska Institutet

Mahmood Jeddi-Tehrani (36)
Avicenna Research Institute

Giuseppe Masucci (34)
Karolinska Institutet

Eva Kimby (32)
Karolinska University Hospital

http://www.researchgate.net/profile/Hakan_Mellstedt

-----------------------------------------------

Now one of the last posts spoke of possibly "Mahmood Jeddi-Tehrani" is one of the reasons why Peregrine has the sudden rise of followers from the Middle East regions, because Dr. Jeddi-Tehrani is based in Iran.

For now though... lets look at Peter Ragnhammar and he happens to be on a very recent publication with Peregrine KOL Hakan Mellstedt and its all based around ones immune system and well, we are entering the immunotherapy age of medicine so I think its relevant and since Hakan was brought on board with Peregrine and Bavituximab is a PS Targeting agent which reduces MDSC's and provides that optimal boost to ones immune system, maybe connect the dots are in order:

---------------------------------------------

Induction of Anti-Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (Escherichia coli-Derived) Antibodies and Clinical Effects in Nonimmunocompromised Patients

Authors: Peter Ragnhammar, Heinz-Jurgen Friesen, Jan-Erik Frodin, Ann-Kari Lefvert, Moustapha Hassan, Anders Osterborg, and HAkan Mellstedt

The pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy.
..
..
pg 7 of 11 -- See Table 4.. breaks down MDSC's (white blood cells)
.

pg 8 of 11 ** ...The results are in agreement with the notion that GM-CSF mainly affects maturatiodproliferation of hematopoetic cells of the myeloid and monocytic lineages. An alternative explanation to the lower leucocyte counts at subsequent cycles may be a decreased capacity of bone marrow to be stimulated by GM-CSF. Moreover, at cycle IV, systemic side effects of GM-CSF (myalgia, fever, rash/pruritus, conjunctivitis, headache, and nausea) were markedly reduced as compared with the previous cycles, which may be related to the induction of anti-GM-CSF antibodies.

http://www.bloodjournal.org/content/bloodjournal/84/12/4078.full.pdf?sso-checked=true

-----------------------------------------------

For those that have not been following WBC = white blood cells vs MDSC's vs cancer..etc, I'll post the link below just to refresh those memories:

For years, researchers have known that a diverse group of white blood cells called myeloid-derived suppressor cells (MDSC) are more abundant in cancer patients than in healthy individuals.
..
..
"We have identified the monocytic cells as the important cell to target, not only in cancer but possibly for treatment of autoimmune disorders like rheumatoid arthritis or inflammatory bowel diseases where dampening the immune response could provide relief," said corresponding author Peter Murray, Ph.D., a member of the St. Jude departments of Infectious Diseases and Immunology. "We also identified growth factors and other molecules essential to the survival and function of these monocytic cells. Targeting these molecules could lead to more precise approaches for controlling the immune response at the tumor site.

"This study marks a significant step in efforts to understand, develop and optimize immunotherapies for treatment of cancer," he said.

http://www.stjude.org/murray-t-cell

-----------------------------------------------

I thought I remember seeing that St. Jude article most recently... posted about it 12/20 and this is what happens when juggling puzzle pieces from every corner of the earth, even Australia... where Dr. Murray is from! and yes, the same Australia where Peregrine decided they needed a 50k Ball Room and a boat load said it was a waste of money. We shall see about that : )

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=109246804&txt2find=murray|st|jude