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Rutgers’ Dr. Raymond Birge+Peregrine 9-26-16 AACR-CRI/NYC Poster, “Characterization of a PS, TAM Receptor (Tyro3, Axl, Mertk), PDL1 Axis in Breast Cancer”. That would be interesting to see the full article, Cheynew.

On 9-26-16, Rutgers’ Dr. Raymond Birge w/Peregrine co-authors, AACR-CRI/Sept26/NYC Poster. This involves Peregrine’s “preclinical I-O focused internal efforts”, which Jeff Hutchins (VP/PreClin.Res) described in the 9-8-16 CC as, “advancing well, and we have seen impressive signs of activity with new combinations of PS targeting and other treatment modalities such as checkpoint blockers, T-cell agonists and radiation.” - see Dr. Hutchin’s 9-8-16 comments below. Note that Dr. Birge is the Senior Author of B119.

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Sept25-28 2016: “2nd CRI-AACR-CIMT-EATI Intl. Cancer Immunotherapy Conf.”, NYC
“The pgm will focus on “Translating Science into Survival” and feature talks from more than 60 leaders in the field covering all areas of inquiry in cancer immunology and immunotherapy.”
http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=101
ABSTRACTS: http://www.cancerimmunotherapyconference.org/abstracts
9-26-16 5:15-7:45pm: Poster Session B
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Track: NEW AGENTS AND THEIR MODE OF ACTION IN ANIMALS AND HUMANS
I. #B019 “LAG3 is an Immunotherapeutic Target in Murine Triple- Breast Cancers, Whose Activity is Significantly Enhanced in Combination with Phosphatidylserine Targeting Antibodies”
Michael J. Gray, Jian Gong, Jeff Hutchins, Bruce Freimark (Peregrine Pharmaceuticals, Dir.Res/Preclin.Oncology)
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Track: MECHANISTIC MERGING OF TREATMENT MODALITIES
II. #B119 “Characterization of a Phosphatidylserine, TAM Receptor (Tyro3, Axl, Mertk), PDL1 Axis in Breast Cancer”
Canan Kasikara 1, Sushil Kumar 1, Ke Geng 1, Viral Davre 1, Cyril Empig 2, Bruce Freimark 2, Michael Gray 2, Kyle Schlunegger 2, Jeff Hutchins 2, Sergei V. Kotenko 1, Raymond B. Birge 1
1=Rutgers, New Jersey Medical School, Newark, NJ
2=Peregrine Pharmaceuticals, Tustin
#B119 ABSTRACT 9-26-16:
http://cancerimmunolres.aacrjournals.org/content/4/11_Supplement/B119
Tyro3, Axl, and Mer (TAMs) are 3 homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (PROS1) and Gas6, and act as bridging molecules to promote PS-mediated clearance of apoptotic cells (efferocytosis). In recent years, evidence has accumulated that TAMs are overexpressed in a wide array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo and radio resistance to targeted therapeutics. TAMs have also been implicated as inhibitory receptors on myeloid-derived cells that suppress anti-tumor immunity. In addition to TAM overexpression, externalized PS is also concomitantly up-regulated in the tumor microenvironment, suggesting that PS & PS receptors might act as immune checkpoint inhibitors. To better understand the biology of TAMs, and the specificity of interaction between TAMs & PS, we generated chimeric TAM reporter cell lines comprised of the extracellular domains of each TAM fused to the intracellular domains of the IFNR1, as well as cell lines stably expressing full-length native TAMs. Using these systems, we found that each TAM receptor has a unique pattern of activation by GAS6 and PROS1, as well as unique dependency for PS on apoptotic cells, PS liposomes, and exosomes. Interrogating epithelial cells that express WT TAMs, we also observed that each TAM showed differential capacity for efferocytosis, AKT-mediated chemo-resistance, and their ability to up-regulate the immune checkpoint inhibitory ligand PD-L1 on breast cancer cells. Functionally, TAM-mediated efferocytosis and PD-L1 up-regulation could be partially blocked by PS targeted antibodies 11.31 & bavituximab, suggesting the existence of a PS/PS-R (TAM-receptor)/PD-L1 axis that drives immune escape in solid cancers. These studies demonstrate that, despite their similarities, Tyro3, Axl, and Mertk are likely to perform distinct functions in both immune-regulation and the recognition and removal of apoptotic cells. Finally, these studies provide a rationale for combinatorial therapeutics targeting PS, TAM, and PD-L1 as immune checkpoint inhibitors in the treatment of cancer.
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9-8-16 CC/Jeff Hutchins: “I would now like to provide an update on Peregrine's preclinical I-O focused internal efforts and our collaboration with Memorial Sloan Kettering CC. The goal of this work is to evaluate combinations of PS targeting with other checkpoint inhibitors and immune stimulatory agents for the purpose of developing new and increasingly effective anticancer treatments. These programs are advancing well and to-date, we have seen impressive signs of activity with new combinations of PS targeting and other treatment modalities such as checkpoint blockers, T-cell agonists and radiation. These new combinations are improving overall survival accompanied with increases in cyto-reactive T cells into the tumor tissue. This exciting new internal work will be presented at the CRI/AACR Immunotherapy Meeting in NY later this month and at ESMO in early October. We expect the first results from our collaboration with the Wolchok Lab investigators to be presented at SITC in November and we will provide more detailed information as that presentation becomes available.” http://tinyurl.com/jydtkoy
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2-2016: Rutgers' Dr. Raymond Birge's relationship with Peregrine & UTSW's Dr. Rolf Brekken and his 2-26-16 article, “Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer” http://tinyurl.com/z5d9qt9 poster B019, “LAG3 is an Immunotherapeutic Target in Murine Triple- Breast Cancers, Whose Activity is Significantly Enhanced in Combo with PS-Targeting Antibodies”

11-9-15 SITC'15: New Bavi+Checkpoint Inhibitors preclin. data (UTSW/DUKE's Herbert K. Lyerly) http://tinyurl.com/pbof95w
...Also, collab. with Dr. Bernard Fox (Immunotherapist/Earle A. Chiles Res.Inst.) on new Immuno-Profiling Clinical Test (Opal 6-plex quantitative IF Assay), PPHM roundtable with Raymond Birge (Rutgers), Douglas Graham (Emory), Dmitry Gabrilovich (Wistar), Rolf Brekken (UTSW), Maria Karasarides (AstraZeneca) - ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.”
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...Dr. Raymond Birge has authored ~85 scientific publications in molecular & cancer biology. http://www.ncbi.nlm.nih.gov/pubmed/?term=birge+rb
“The Birge laboratory conducts basic science focused on the eradication of cancer.”
http://birgelab.org => http://birgelab.org/biography.html