MSB 2023 - awaiting for Ryoncil approval, page-187

Interferon Gamma and TNFR-1 look both to be involved in the T cell proliferation or activation.

I think its important to be clearer about terminology than that. T cell proliferation is essentially T cells becoming more numerous, growing in number. If a particular T cell whose function is to attack foreign objects gets activated (by detecting something foreign with its particular foreign detection receptor (which is essentially unique for itself) then it can also being so activated, start to grow and divide to form more of itself to increase its effectiveness in going after what is foreign - this is essentially what happens (in simple form) in Graft versus host disease.T cells from the graft think part of the host is foreign and they become activated so grow and then divide into two to form more of them to be better at attacking the foreign thing. This is only sort of right. But I'm trying to make clearer what happens with T cell proliferation. Proliferation is more of the same tupe of T cell that's doing the attacking of the foreign thing as it sees it. And conversely inhibition of that is stopping or reducing that proliferation.

If you look again at the MSB slide I just posted above with the cartoon of remestemcel_L on it as well as INF Y and TNFR1 and understand that what is labeled CD4 ad CD8 are T cells then you can see an a sort of grey arrow going from IDO in the remestemcel-L cell to the CD 4 T cell that has a flat end on it like a T intersection rather than a pointed arrow. That is the way science papers and text books show inhibition or down regulation or blocking as opposed to an arrow head which would suggest stimulation or signalling or activating or up regulation (making more of versus making less of).

I'm writing this partly for the benefit of possible other readers looking at MSBs slide.

Are there any studies that looked at both at the same time and not just 1 or the other ?

Yes. The 2021 Klinker and Bauer article I've been referring to and which you apparently haven't read or looked at yet use various dosages of TNF-alpha (TNF-alpha does go through the TNFR1 receptor) and INF gamma to prime four different cell lines of MSC cells and they use various doses of the TNF-alpha and INF-gamma on each of the four different MSC cell lines.

Now Klinker and Bauer's paper might not look like an exact hit that's relevant to many MSB holders that don't care much about the science or about potency assays, but the very fact that Klinker is still likely to be involved in MSBs BLA resubmission evaluation and that he has a paper on INF-gamma and TNF-alpha both being tested in various doses against various MSC cell lines should interest you enough to look at the specific paper.

There will almost certainly be a lot in the paper that if you don't have a bit of a science background you or other holders won't immediately or easily understand. And that's okay. If you make an attempt to understand you can start to get it. But its potency assays, its 2021 (so recent), its MSCs, and its by the guys that have been evaluating your BLA submissions.

But what's not okay is not looking or pretending that Klinker writing on INF-gamma and TNF-alpha in terms of MSC potency and priming is not relevant.

There are rich sources of information available that a lot of MSB holders and frequent commenters here are not engaging with at the same time as they are claiming over and over that no one else can know what they don't know because they won't look.

There is a quote from Arthur Conlan Doyle's Sherlocke Holmes - when you eliminate the impossible, whatever remains however improbably, must be the truth.

What is happening on the MSB forum is that many holders and traders and socialites are not learning and reading enough to eliminate the impossible - on the contrary they are staying ignorant through choice or unwillingness to read and learn - so not getting to what must be the truth (they claim there isn't enough information we all just have to wait, none of know anything they say) - whilst at the same time attacking the character or motives of those who are wanting to look at the data to eliminate the impossible to get to the truth.

I'll look for the link to the Klinker and Bauer 2021 article again - the full article is available in the public domain - I have linked to previously, but the way I interact with the HotCopper website (through Tor Browser) makes it hard for me to get access to everything all the time. I have to keep logging in and out.