NorthWest Biotherapeutics Inc (NWBO)

[Doktornolittle]

Mesenchymals mostly unmethylated? That is what I think I am hearing from LL starting at 46:35 in this excellent video that was posted yesterday (maybe posted prior also but that was the first time I saw it).

Even LL and the other researcher here had some difficulty making it clear which genetic type they are referring to, methylated vs unmethylated, so I may be misunderstanding. But if not...

Years ago I was angry that the FDA forced SOC on DCVax-L given that TMZ is known to damage the immune system to the point of immune system collapse being the ultimate cause of death in most patients. But without an immunotherapy adjunct, that is not as horrible as it sounds, quality of life aside. I grew to understand and accept that.

But even accepting that TMZ does add life in spite of this damage to the immune system, it remained totally unclear why it was being prescribed to patients that are of unmethylated genotype. Maybe they didn't have a good way to test for that back then? But I think they did. This remains a question in my mind. You can always find one study that says TMZ (in this case) works a little bit for the unmethylated types... but I think there are many studies that say it only helps for the methylated types, and it damages the immune system for both types, and reduces quality of life for both types... so why in the hll was it ever prescribed for everyone to begin with?

Now bring on immunotherapies for GBM. Now the amount of TMZ that is likely optimum almost certainly reduces. And the use of it in the unmethylated population becomes even more glaringly improper.

If I understood LL correctly that the mesenchymals are mostly unmethylated then dropping the use of TMZ for the unmethylated population will likely have a very large positive impact for DCVax-L both in terms of efficacy and patient quality of life.

But... I may have flipped this methylated, unmethylated, TMZ responsive, TMZ unresponsive relation somewhere in here.