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Interesting dialogue between beej (new/fresh to SA) and Plainview (short author), looking forward to read respond to this (if at all)!!!!!
< beej3000
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It is not at all the same conditions, at all. With time I could come up with hundreds of other factors not accounted for a in a tightly controlled in vitro experiment. Including but not limited to cell-cell interactions between APCs, CD4s, and hundreds of cytokines that could cause an exponential systemic effect downstream.
You make your main point about plain ol' IL2 and how it's better. Are you under the assumption that the initial targeted cells by 214, the ones those effect downstream won't produce IL2 and other stimulatory effector cytokines? This is the immune system we're talking about here. All components are interdependent on cell to cell interactions and soluble factors that initiate exponential effects through downstream signaling cascades.
To your first point. The second article I referenced (taken from you) blatantly states there is a positive correlation between increased in vivo Ki67+ and peripheral cell counts. As stated in the quote I provided in my original post. In your analysis, did you consider that paper is looking at acute proliferation in an AIDS model? Don't you think long term proliferation and sustained effector function is valuable, and even more relevant in this case?
I have another question for you. Why did you manipulate the graph taken from the ASCO 2017 poster? You altered the Y-axis to display the same units of the Y axis in the Rosenberg paper. Not only can one see that they are not in the same range after simple dimensional analysis, it's also just plain dishonest.
Another thing about your comparison to that article. That dramatic increase in T cells (I believe your claim was 200-300%) in comparison to the figure you manipulated were 91.1% suppressive Treg cells per Figure 5A of the very same article. Doesn't make that little increase in Tregs you mentioned from the poster presentation so bad, now does it? That also goes back to my point that once you stimulate T cells with 214, they're probably producing IL2 which will inevitably bind Tregs, among other cells and spur a response.
IL2 binds IL2Rbg (Ts, NKs) and IL2Rabg (Tregs). 214 has much higher affinity for the bg variety (beta gamma) by about 1000 fold. The goal of this whole thing is to SELECTIVELY boost the immune system, which is what it seems to do. What is it going to do at the end of Phase 3? I can't say, time will tell.
03 Oct 2018, 10:30 AM |
