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Are you sure about that Wook?
See CJ's post from 10/14/14
A year and two months into the p3 NSCLC trial and Peregrine is saying they are on schedule with enrollment, with 33 & 50% look-ins, does this satisfy any doubt in regards to them achieving what you said they would never do?
Is this less transparent and believable in regards to achieving full enrollment?
(Yes iam aware of their history)
All the best,
John
BioBs,
The study is interesting in that inhibitory immuno mechanisms are mitigated with combination therapy. All responding mechanisms were downstream and non redundant as opposed to a redundant immune responses. The combo actually looks promising in that it could aliviate Tcell anergy, which is common when releasing the breaks on tcells without antigen reception. It's a focused stimulation, IMO.
Would I be labeled a "homer" if I suggested adding Bavi to create the dream combo? Of course you would want Bavi initiated first, IMO :)
All the best,
John
If CD47 is exposed (expressed) on tumor cells and elicits a "don't eat me" signal to avoid immune surveillance, then theoretically wouldn't anti-CD47 antibodies achieve the very same MOA as Bavituximab?
Unraveling this cloaking concept is part of Bavituximab's MOA, and there seems to be synergy with combo antiCD therapy. However, it also brings to light a duplicate mouse trap or redundancy, IMO..
All the best,
John
Had a package of refrigerated Bevacizumab in (my) hands yesterday, and for a moment I thought it read Bavituximab... The mind plays tricks sometimes..
I also remember the old MOA too..
All the best,
John
WH,
Please post more often. I've enjoyed reading your post when I have time.
Nuke Med..
Remember Dr Thorpe's patent and PE nuke imaging using biotinylated duramycin to detect apoptotic events, which include both imaging and therapeutic properties??
Someone still has interest in the science..
Molecular Imaging of Apoptosis: From Micro to Macro
Wenbin Zeng1?, Xiaobo Wang1, Pengfei Xu1, Gang Liu2, Henry S. Eden3, Xiaoyuan Chen3?
1. School of Pharmaceutical Sciences, and Molecular Imaging Research Centre, Central South University, Changsha, 410013, China;
2. Centre for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,
School of Public Health, Xiamen University, Xiamen, 361102, China.
3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health, Bethesda, Maryland, 20892, USA.
? Corresponding author: wbzeng@hotmail.com (W.Z.); shawn.chen@nih.gov (X.C.).
© 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
See http://ivyspring.com/terms for terms and conditions.
Received: 2015.01.09; Accepted: 2015.02.18; Published: 2015.02.20
Duramycin, a
19-amino-acid, disulfide crosslinked peptide has been
found to be capable of binding to PE with high affinity
and high selectivity [88]. Duramycin is covalently
modified with HYNIC and labeled with 99mTc using
the tricine-phosphine coligand system. With its robust
binding mechanism and favorable pharmacokinetic
profile, the in vivo properties of 99mTc-Duramycin are
promising [89-91]. However, up to this point, HPLC
purification is prerequisite for intravenous injection.
Therefore, it would be desirable to attain high quality
99mTc-Duramycin without additional purification
steps in a single-step kit formulation. Recently, a single-step
kit formulation was developed for
99mTc-labeling of HYNIC-Duramycin [92]. An optimal
formulation with tricine-to-TPPTS molar ratio of 10:1
was ultimately determined, which led to consistent
production of 99mTc-Duramycin with high radiochemical
purity without need of further purification.
The radiopharmaceutical produced retained PE
binding affinity and specificity, while its clearance
properties and in vivo biodistribution were consistent
with those in prior studies involving radioHPLC-purified
preparation [91].
In addition to exposed PS and PE, recent studies
indicated that the exposed histones on the cell surface
can also be one of the characteristics of apoptosis [93].
Based on this, Wang et al. identified a CQRPPR hexapeptide
(Apopep-1) using phage display technology,
which targets the histone H1 exposed on the surface
of apoptotic cells [94]. Modification of ApoPep-1 with
radioactive iodine (124I) enabled PET imaging of tumor
apoptosis in vivo. The uptake of 18F-FDG decreased
only by 0.97 in drug-induced apoptosis of
tumor
http://thno.org/v05p0559.pdf
References
Zhang L, Zhou H, Belzile O, Thorpe P, Zhao D. Phosphatidylserine-targeted
bimodal liposomal nanoparticles for in vivo imaging of breast cancer in mice. J
Control Release. 2014; 183: 114-23
MD
I'm glad we have a physician on board here helping to legitimize Bavituximab. I just assumed you were a doc but also noticed your first post on Ihub. Were you doing residency when you met PT?
Anyone sell shares into today's rally? MD?
The reason I ask is that many times these types of articles, either pro or con involve such action.. Although I like good articles and good honest opinions regarding Bavituximab, it still lacks the peer reviewed respect that is needed here. This article as many pump or bash articles do, lacks legitimacy, IMO.
I'm not trying to admonish anyone and appreciate the efforts, but if history holds true then we'll be back where we started in short order, unless of course the Calico Family deal comes true :)
All the best,
John
Just FYI,
Some of the transcending synergy is related to a common receptor, RAGE. The rest is conceivable from there.
All the best,
John
You and me both PG!
All the best,
John
AGE as in Advanced Glycation Endproducts.
This precludes many other age related synergies with Bavituximab, IMO..
All the best,
John
That would be fundamentally and functionally impossible and false, IMO. The idea would (be) to use both in conjunction to radiotherapy and or chemo.
Cotara targets intracellular antigens whereas Betabodies have affinity to extracellular lipids. Both are armable and have the potential to deliver cytotoxic agents, however the fundamental roadblock lies in their pathway to target. Cotara is injected directly into tumor core, whereas Betabodies would be intravenous. The major point being that Betabodies armed with TNT wouldn't be deliverable. Not to mention impossible as both are MAbs..
All the best,
John
MD,
I look forward to your next article... Good stuff..
All the best,
John
As talented as CP is it surprises me that he would theorize as such. It has me apprehensive in my knowledge and reluctant to challenge him, but I don't see it as possible.
I've got a few ideas as to why Melanoma might be the ideal target for Bavituximab. Whats your opinion on the pharmacokinetic synergy and Bavi in this indication?
All the best,
John
Regarding BBB & passage.
Although size does matter when penatrating BBB, what's more important is having a "ticket to ride".. That's why being bispecific helps and makes it possible for Betabodies..
All the best,
John
Sulaco,
Yes, IFNa, IFNg, IL12 are immunostimulatory and IL10 was mistakenly decribed as well, as it should have been immunosuppressive.
Thanks, and all the best,
John
Cloaked Protecter,
CP,
Maybe CP meant eminent, as a clue? eminent domain, a compensatory bid for liver indication?
LOL, read between the lines..
All the best,
John
At CP's expense..
We've all made typos.
All the best,
John
Phosphatidylserine is a non-polymeric phosphalipid macromolecule. The molecular genetic biosynthesized structure would be "PTDSS1", and is absent from poorgradstudents gene list on the BV board. However, there are several other PS associated pathways amongst the list, including NOTCH1, NOTCH2.
I also noticed that the TIM receptor family to be absent as well, which is rather interesting, and builds credence that the gene list is not the "be all, end all" of recognized genetic physiology.
I can say that because several BP's are currently working with the TIM family, of which by the way are Phosphatidylserine associated receptors.
All the best,
John
North4000,
They are going for an early approval based on PFS.. This is Garnick seeing the forest through the trees, and is his style..
It's my opinion that PFS is a better, more pure means of measurement in second line trials. It eliminates bias from previous treatment.
This also fits more precisely of what Bavituximab is, a preemptive vaccine..
Looks like Accelerated Approval based on PFS is being set up..
All the best,
John