NorthWest Biotherapeutics Inc (NWBO)

[Doc logic]

Umibe5690,

Methylation status is one of the ongoing scientific discussions because of the variation in strength within various patients. There are examples of multiple attempts to define at what point methylation becomes significantly important in the various patient groups based on treatment responses and various posters including flipper44 have shown examples of different cut off points used by researchers to delineate methylation status. In abeta's post contained in this thread you see 6 different methylation groups. What I can say with certainty is that methylation levels will make a significant difference depending on the type of treatment received. With Temodar the classical GBM subtype seems to respond the best. With radiation, meth+ seems to help some others a little bit but not to a significant level in all cases. With DCVAX-L both methylated and unmethylated seem to be observing an advantage. So as any given treatment is able to affect certain gene function or expression, methylation becomes more or less important. DCVax-L seems to potentiate immune response and positive gene expression against significant targets to the point where methylation status (strength across a spectrum) is important but only part of the total antitumor action taking place.

Dr. Linda Liau and others considered a methylation cutoff at a different point than others and I have seen indicated in earlier research that meth+ mesenchymal is indeed in the mix but most certainly methylation different than what is seen in typical proneural. Also if you look at abeta's 1st two pie charts the proneural and mesenchymal subtypes are significantly different based on whether histology is validated or not. I go with histologically validated percentages which puts proneural at about 13% with a 5% G-Cimp marker group in the mix that takes it up to about 18% if included as a none exclusive group. Obviously if methylated MGMT status is historically considered to be 40% then there is at least 22%-27% additional meth+ outside of proneural. The 100% meth+ seen in that one paper you cite is.. well let's just say trying to stand on it's own two legs which are stilts with one 2 feet shorter than the other. That happens when you try to define the import of methylation or other status by setting up groups in a highly individualized disease where multiple interactions and levels of gene expression play key roles in responses to any given stimulus/signal.

Bottom line as you correctly surmise, L appears to work well in both methylated and unmethylated and Dr. Linda Liau's claim that L is her greatest achievement seems to be well placed confidence in a treatment that she made initial contributions to and appears to have been "optimized" over time. Best wishes.