Just a test

@stanjupiter - I'm replying here stan because I can't be bothered wrestling with the Hotcopper post button processing on the MSB forum - feel free to cross post my reply to you back there if you wish - this is in reply to your post 69307863.

You in bold - my replies in not bold.

You're saying you know for sure there would have been enough parents willing to forgo the "easier option" and place their child in a clinical trial for "the greater good"?

Absolutely is not a word I use loosely - there are few absolutes - but I am very tempted to reply to your question thusly - "ABSO - bloody - LOOTLY". Any parent thinking their child is facing almost certain death would much prefer a chance at saving that childs life than no chance. A fifty fifty chance at the treatment arm is giving every parent of ever child an equal chance at the treatment arm (whatever the treatment arms is).

Parents would have to be given proper informed consent.

@stanjupiter - I like you, sincerely, I see in you a fellow borderline depressed person disillusioned at the stupidity of his fellow man on occasion. But I also think you are ignorant of some basic science and biological realities about viruses and vaccines and cell biology generally so that you attribute to your fellow humans bad judgement when in cases of medicine and science they too are ignorant and doing their best in some cases.

Take a look at the first "successful" randomized trial in GvHD Reach2.

I have NEVER said to you that I considered REACH to be successful. You are bringing up stuff others have suggested in your discussion with me - don't do that please. It will waste both of our precious time.

Were those patients who ended up randomized to two therapies only a moron would have chosen as BAT given proper informed consent? What on earth did this RCT help anyone with reasonable comprehension skills learn that wasn't obvious from Reach1?

I don't know enough about the Reach to have an opinion.

I do know this - doctors do not create cancers (for the most part - chemo and radiation might do that as side effects) - they try to cure them. When GvHD arises as a result of a attempt to cure a patient of cancer (kid or adult) that is not the fault of the doctor -that is an unfortunate accident as a result of a lack of human know-how to avoid that at this point in history - a child that says to a doctor - you gave me this, you fix it - is a child talking like a child and blaming an adult, a doctor, that is also a bit like a child, trying to do the best with the tools at his or her disposal. The doctor did not intend to do the child who gets GvHD harm - he or she intended to try to help the child.

I know that you come to this message board with some well formed long held opinions about vaccines and about other treatments and about inconsistencies in approach - I don't know whether those opinions of yours are well founded or not - I simply don't know, they might be prejudices you carry around for all I know - I can't unpack all your baggage - I can sympathise with your distress at the state of the world though.

By doctors aren't the cause of GVHD. And randomised controlled trials whilst not alway necessary (sometime as knowledge gets greater lab tests may more quickly and efficiently zero in on mechanisms of action) they are in my experience never motivated by anything other than a desire to learn how to treat all those with the disease better in future.

Doctors don't create illness and injustice as a generalisation. They generally try to fix it. Some times they absolutely stuff up. For 2 and a half centuries bleeding patients was standard medical procedure - the docs didn't know any better. They had to learn.

Originally posted by JB1975: ↑

You in bold (me responding to dachopper's post 69258225 dated 10 Aug 23 - reposting (if second attempt fails) to test forum because some block on the post handling is preventing posting to the MSB forum at present in the means I am trying to use).

What happens if a patient who has a MAP score > 0.29 recieves an INF Gamma increasing MSC, and then survives?--- Respectfully, (and yes, I did see your post after this one with the graphics and I do know that you've faithfully sourced some MSB material (but I don't think its relevant to your question) (and Ihad seen that research before), your question seems tangled up to me.

Are you suggesting that you know of even a single circumstance in real life where "a patient who had a MAP score > 0.29 received an INF-gamma increasing MSC and then survived"?

Because I don't think that would have been investigated or done because I think that is not what the MAP score is about - its a surrogate biomarker for survival (its in that sense (as a surrogate biomarker for survival - and certain not as a potency assay) that its authors and patent holders claim for it to have been validated) - its not a potency assay at all, let alone a validated (in someone's opinion or through demonstated methodical science in a peer reviewed journal) potency assay.

Unless things have changed in the last 18months to 2 years the FDA allows certain biomarkers to be registered with it. But they don't have to be. MAP isn't or wasn't last I looked. Validation of a biomarker can be done on the strength of the science demonstrated in scientific papers - and it is in that sense not the registered with the FDA sense that the MAP score stuff is said to have been validated - (and I largely agree - I read a bunch of the related papers - it looks to be pretty validated to me - but its got limits - and it has nothing to do with MSBs two part matrix approach to potency assay validation.

I stress this important point to you -- A validate surrogate biomarker for survival (the MAP score) is a different thing entirely to a validated potency assay (though both have the word validated in them and both involve things that can be measured in blood samples). I think you get that - but your question suggest maybe you don't completely. There is no relationship I can think of off hand between ST and reg3a blood levels in blood (which is what the MAP score is working with) and TNFR1 and IL2Ralpha (CD25) which is what the potency assay matrix approach (as disclosed by MSB) are concerned with. Two tools for two different purposes.

If you agree with and understood already that they were two different things/tools for two different purposes than your question to me looks very strangely constructed - like it is you not me that is constructing a strange hypothetical.

When MSB wanted to show a relationship between their potency assay component IL2Ralpha in vivo and in vitro - they did it with blood samples taken from some eleven or so patients in the GVHD001 trial for which they had information on both the single lot amounts of IL2ralpha amounts and the before and after (specifically I think it was 28 days after) blood readings in the patients of that same molecule (ie CD25 - so not ST or reg3alpha) as measured on FACS (florescent activated cell sorting - sometimes called flow cytometry) readings. This is a slide I've referred to on several occasions previously it has an r2 of 0.35 only from memory and as shown by MSB doesn't scale the horizontal axis correctly.

Here it is - (this slide cc-32 has some of my comments on it - not sure if I've posted it before with my comments or not).

Currently there is no in Vivo evidence that a cell that does or even does not decrease Inf Gamma has any effect on survival - so you are postulating that an unproven hypothetical would cause concern over what is now becoming proven in Vivo survival data?
One is theoretical, the other is practical data.
That statement of yours that I've highlighted in yellow is one heck of big statement by you! And you include it as part of a longer sentence that also includes a characterisation of my position (that I'm postulating an unproven hypothesis) which you do at least have the courtesy to express as a question.

Have you googled to check my claim that INF-gamma was once called macrophage activating factor ? - I could be wrong remember, (***) but if I'm right there would have been some process by which it got that name. And it easily could have been by doing some work with INF-gamma and macrophages in vitro (meaning essentially in a lab dish as opposed to in vivo) but if something happens in vitro (say INF gamma has an observable effect on a macrophage) then that would be SOME evidence that it likely could also happen in vivo. Stuff that happens at the cytokine level between cytokines and specific types of cells in vitro is also likely to happen in vivo -because molecules are molecules.

(***) I just jumped onto another computer - because I post to Hotcoper in Tor browser and don't want all the HC advertisers tracking me about - I have to use another computer to cross check some facts - "when i put "macrophage activating factor" and "interferon gamma" together on my laptop I go straight to a 19 June 2018 nature reviews immunology article. "IFNy: signalling, epigentics and roles in immunity metabolism, disease and cancer immunotherapy"

One can reduce IL2R alpha by around 80%, the other in contrast cause minor increases and decreases to INF Gamma < 30%.How can you possibly know that swings of up to 30% INF gamma in an in vitro scenario (that is when one lot of MSB MSCs is added versus another lot or versus it not being added at all) is minor when that same product is put into a patient?

Look I apoligse for the poor structuring and repetitiveness of some of my posts but previous experience has made me doubt the wisdom of spending a lot of time post polishing to make the post read easier. That both previous experience with you - who I have not found to be particularly appreciate of the efforts I've made with you and previous experience with the forum - I've previously gone to some efforts to post science specifics and have someone like pledge repost exactly what I posted to someone like gav--66 as if it was an example of pulling the wings of flys - when had pledge only taken the time to try to understand it he might have learned some useful cell biology that directly related to the likelihood of MSB getting a BLA. This has happened to me a lot and I often feel I have not invested my time and effort in the right places and with the right people on the basis of how they have responded when I thought I was generous with them. @dachopper - if you want feel - if you feel others will get something from seeing this or continuing this discussion in the forum I tried to post it feel free to repost it - I'm just too impatient at present to buggerize around with hotcoppers post button processing on the MSB forum.

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