GVHD the first step, page-95

@dachopper

I don't recall them nominating (naming) TNFR1 as the potency assay that they'd linked to survival, I remember them talking in more general terms like the potency assay they'd used in the GVHD001 trial, or the 54 patient pediatric trial, was linked to survival.

That it had to be TNFR1 is pretty much my point - I don't think they've actually said what it was - could be wrong as I'm working from memory now not checking.

I do think TNFR1 is linked to survival in that it activates the NFkappaB pathway - Doronsoro was the pioneering science paper on that and it was cited in MSBs ODAC papers. I regard that as solid science. Saying either TNFR1 or "the potency assay that was used in the trial" has been linked to survival - just means they've found some data that suggests a correlation to something like T cell proliferation inhibition in vitro and possible something like more TNFR1 expression readings being associated with better survival.

T cell proliferation is such a commonly accepted (and sensible in my opinion) in vitro measure that most people would assume and expect a link between T cell proliferation inhibition and survivial.

If the T cells which are the immune cells can't proliferate they can't cause GvHD - they need to be able to do that.

Thing is though if you put mesenchymal stem cells into an in vitro testing enviroment with T cells then (as MSBs own slides CC-22) show the CD8 t cells can produce interferon gamma which IDO in the mesenchymal stem cell responds to and that has the effect of inhibiting CD4 T cells.

MSB could report having linked either TNFR1 or more generally the potency assay they'd previously used to survival - meaning to T cell inhibition - and it wouldn't necessarily be enough if there was also INF-gamma right along side it also doing the same T cell proliferation inhibition and they never measured it.

You are free to believe whoever or whatever you want. But I don't own the science, neither does MSB, neither does the FDA, and science isn't a matter of belief,its a matter of discovery and analysis and understanding the evidence.