Friday, May 31, 2019 9:09:09 AM
Like ALL drugs, Mechanism of Actions can be learned, fine tuned and realized
Bavituximab is one that is unique and we are square in the middle of Biomarkers and protein pathways that are affected by where dozens of downstream actions occur all initiated by some global, upstream action ....and of course, there is nothing better than live, 3D imaging....where FDA officials can not deny that the Targeting of Flipped PS PtdSer Phosphatidylserine occurs ....and that sets off a series of events
I have been tracking many events over the years including hundreds of key thesis papers that are approved by key players in academia
There is simply no time to post the most important ones re: IO drugs etc etc but what is important is that the FDA will receive some major backlash with continued, corrupt like actions that side with some within Big Pharma
What future expansions at Avid are based upon PS Targeting IP?
I like the words "upon activation" because there are hundreds of academia type research that is approved by key researchers ...and if we compare to Bavituximab....the events that occur AFTER PS Targeting will disrupt Big Pharma as we officially have been forced, to know it.
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Bavituximab MOA
https://www.xvivo.net/animation/bavituximab-mechanism-of-action-moa/
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Kole Thomas Roybal - UTSWM Thesis
T cell activation occurs through interaction with an antigen-presenting cell (APC). Upon activation, signaling ensues with the coordination of dozens of diverse signaling molecules in space and time, a feature of cell signaling we call ‘spatiotemporal patterning’. We performed a systems-scale analysis of the spatiotemporal patterning of T cell signaling and have found that it is highly diverse. Over 50 signaling sensors were imaged in live primary T cells activated with APCs under various physiological stimulation conditions, and no two signaling intermediates showed the same dynamic localization. The activation environment controlled spatiotemporal features of T cell signaling and specific spatiotemporal features correlated with efficient T cell activation. To identify underlying cell biological mechanisms controlling spatiotemporal organization of signaling, we complimented our live cell imaging with microscopy across multiple scales and identified a dense transient F-actin network that extends from a highly interdigitated T cell:APC interface several micrometers deep into the T cell lamellum. Systems-scale imaging revealed a large network of proximal T cell signaling intermediates that localized to the lamellal actin network and shared the spatial, temporal, and mobility features of F-actin. Interference with lamellal actin dynamics modulated the activity of the associated proteins and impaired IL-2 production. These data strongly suggest that the transient deep F-actin network by controlling lamellal localization modulates the activity of a substantial part of the T cell signal transduction system. As a next step in understanding how spatiotemporal dynamics of signaling controls T cell activation, we have developed a quantitative 4D analysis approach for signaling networks and coupled it with traditional cell biological techniques to uncover higher order mechanisms of the control of actin dynamics by CD28 co-stimulation during T cell activation. A group of nine actin regulatory proteins that mediate actin polymerization, capping, and severing were assessed and CD28 co-stimulation was required for their sustained activity at the T cell:APC interface. WAVE2 and Cofilin were especially sensitive to blockade of CD28 signaling. Functional relevance of the loss of WAVE2 and Cofilin enrichment was shown by the treatment of T cells with constitutively active Rac1 and Cofilin, which bypassed the requirement of co-stimulation for normal actin dynamics and AKT activation. This study highlights how a systems analysis of actin regulation could identify mechanisms that are inaccessible to more traditional single protein/gene approaches.
https://utswmed-ir.tdl.org/handle/2152.5/1587?show=full
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Interesting, Bavituximab mentioned in this patent like as if, many know it is required for CAR-T therapy to avoid those Cytokine Storms / Cytokine Release syndrome ...as Dr Jedd Wolchok KNOWS
BINDING-TRIGGERED TRANSCRIPTIONAL SWITCHES AND METHODS OF USE THEREOF
Publication number: 20180355011
Abstract: The present disclosure provides binding-triggered transcriptional switch polypeptides, nucleic acids comprising nucleotide sequences encoding the binding-triggered transcriptional switch polypeptides, and host cells genetically modified with the nucleic acids. The present disclosure also provides chimeric Notch receptor polypeptides, nucleic acids comprising nucleotide sequences encoding the chimeric Notch receptor polypeptides, and host cells transduced and/or genetically modified with the nucleic acids. The present disclosure provides transgenic organisms comprising a nucleic acid encoding a binding triggered transcriptional switch polypeptide and/or a chimeric Notch receptor polypeptide of the present disclosure. Binding triggered transcriptional switch polypeptides and chimeric Notch receptor polypeptides of the present disclosure are useful in a variety of applications, which are also provided.
Type: Application
Filed: December 4, 2017
Publication date: December 13, 2018
Inventors: Wendell A. Lim, Leonardo Morsut, Kole T. Roybal
https://patents.justia.com/inventor/leonardo-morsut
https://patents.google.com/patent/US9670281B2/en
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