Replies to post #139706 on NorthWest Biotherapeutics Inc (NWBO)

[Extremist223]

Constant learning every day Senti. There is a youtuber called "Shomu's Biology" and he has lectures that will give you the basics on antigen presenting cells (DC's) and how they interact with T helper cells to drive the rest of the immune system.

Fact check me please, but T-cells undergo genetic recombination when they are born, each is unique, and each have unique specificity to some antigen conformation. When major histo-compatibility complex on say a dendritic cell presents an antigen on MHC II to the T helper cell receptor, if the receptor has the right conformation and has a particular affinity to the MHC + Antigen, it will become activated. That process depends on certain cytokines and costimulatory domains. DC's interact and activate t helper cells which can then activate the entire cell mediated adaptive immunity. This includes activating, nk cells, b cells and cytotoxic t cells. The paper I found for you outlines how DC's can take different phenotypes.

https://www.ebi.ac.uk/interpro/potm/2005_3/Page1.htm

"Furthermore, there are thousands of identicalTCRs on the surface of a T cell, which increases the likelihood of binding when an antigen is encountered."

This means that each t-cell born is specific to one conformation.

And what exactly was it that you were wondering TCRs could overlap with? Direct or L? Or an overlapping repertoire of TCRs alone?

So when I question the t-cell receptor repertoire, I mean the aggregate of all the t-cells for their specific conformation. It means that you may receive a dc vaccination, but may not have the proper t-cell floating around. I'm not sure how probable that is, but the answer I think is not impossible. So the overlap between repertoire and presented antigens from DC.

All of this to say that Kite's technology genetically modifies T-cells to have a particular receptor that recognizes 1 unique antigen, which is great when the entirety of the cancer expresses that antigen. We've heard this theory a million times.

This theory of lysate activating against the full repertoire of antigens, if proven true would be the reason that NWBO could be worth multiple billions. Successful results in GBM almost certainly mean successful results in other indications. Gilead is betting on success in CAR-T being transferable to other indications, but they'll have to change the genetic modification tidbit to attack a new homogeneously expressed antigen for each indication.

And can TCR's result in CRS and neurotoxities like CAR-Ts can?

Cytokine release syndrome has been documented in adoptive t-cell therapies. I'm sure dcvax when combined with checkpoint inhibitors could cause too much damage if dosed incorrectly. Which brings me to a question for Flipper!