Replies to post #300359 on Avid Bioservices Inc (CDMO)

[cjgaddy]

Thx BB762: A.Schroit’s 6-22-17 Nature/BJOC Exosomes testing Betabodies

PPHM’S EXOSOMES DIAG. PLATFORM (incl. 6-22-2017 NATURE/BJC article)
...Known POC Data Summary (see below):
1-22-17/OncoTarget: Ovarian – senior author Alan Schroit (UTSW/PPHM SAB)
6-22-17/Nature(BJC): Breast & Pancreatic – senior author Alan Schroit (UTSW/PPHM SAB) *Using Betabody KL15C*

PPHM’s PS+ EXOSOME-BASED CANCER DETECTION & MONITORING TECHNOLOGY ("Liquid Biopsy")
...Excellent Exosome (aka microparticles, microvesicles) info: http://www.exosome-rna.com

6-22-17: Nature (British Jrnl of Cancer): ”Detection of Phosphatidylserine-Positive Exosomes for the Diagnosis of Early-Stage Malignancies [Using Betabody KL15C]”
Raghava Sharma, Xianming Huang, Rolf A Brekken (PPHM SAB), Alan J Schroit
….Dr. Schroit: PPHM SAB, UTSW profile: http://tinyurl.com/yaqnvcvq ; pubs: http://tinyurl.com/lqbd8kt
https://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2017183a.pdf
ABSTRACT
Background: There has been increasing interest in the detection of tumor exosomes in blood for cancer diagnostics. Most studies have focused on miRNA and protein signatures that are surrogate markers for specific tumor types. Because tumor cells and tumor-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker.
Methods: This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumor exosomes in the blood of tumor-bearing mice. To monitor the relationship between tumor burden & tumor exosome plasma concentrations, plasma from one transplantable breast cancer model (MDA-MB-231) and 3 genetic mouse models (MMTV-PyMT; breast and KIC and KPC; pancreatic) were screened for captured exosomal phospholipid.
Results: We show that quantitative assessment of PS-expressing tumor exosomes detected very early-stage malignancies before clinical evidence of disease in all 4 model systems. tumor exosome levels showed significant increases by day 7 after tumor implantation in the MDA-MB-231 model while palpable tumors appeared only after day 27. For the MMTV-PyMT and KIC models, tumor exosome levels increased significantly by day 49 (P<=0.0002) and day 21 (P<=0.001) while tumors developed only after days 60 & 40, respectively. For the KPC model, a significant increase in blood exosome levels was detected by day 70 (P=0.023) when only preinvasive lesions are microscopically detectable.
Conclusions: These data indicate that blood PS exosome levels is a specific indicator of cancer and suggest that blood PS is a biomarker for early-stage malignancies.
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Addl. article info (Fig.1) extracted by Bamboozler762 6-23-17 iHub #300359 http://investorshub.advfn.com/boards/read_msg.aspx?message_id=132436726
Fig1: Schematic diagram of betabody, KL15C
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Note: BETABODIES (Clipped/Nicked B2GPI - ex: KL15, “2nd-gen. PS-Targeting”) - bind to PS directly, are smaller in size (100 vs. 250KDa) and have a longer serum half-life (~5days) than natural antibodies (Bavi=~1day) – see http://tinyurl.com/khopa3d …2/17/15: UTSW/PPHM’s BetaBodies patent#8,956,616 Awarded(Granted) http://tinyurl.com/p75uyfu

Fig.1: Schematic diagram of betabody, KL15C
Domains 1 & 5 of the plasma PS-binding protein, B2GP1, were genetically fused to the C-terminus of the CH3 domains of the Fc fragment of human IgG1. A Gly4Ser linker was inserted between the CH3 domains and domains 1 and 5 of B2GP1. The recombinant betabody was expressed as a dimer.
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...Glimpse of beg. of 7pg. 6-22-17 the Schroit/Brekken/etal BJC article: http://www.readcube.com/articles/10.1038/bjc.2017.183