Hi Abeta:
Mesenchymal is characterised by a deletion of NF-1 and a mutation of the P-53 gene. It is predominantly M-. As Flipper44 pointed out, the mesenchymal population is relatively large and a large study demonstrated that mesenchymal may constitute nearly 50% of all stage IV glioblastomas. Further, Classical is known to respond to DC VAX although perhaps not to the extent of mesenchymal. LL and RP from their clinical experience stated that the vaccine is particularly effective in the mesenchymal strain. They explained their hypothesis by saying that mesenchymal presents many antigen targets and is immunogenic meaning that the tumour micro-environment is less suppressive thus giving T-cells, etc. more time to infiltrate/destroy. Perhaps they may have been premature in their assessment but I highly doubt it. And from the publication, you can see that the blended OS is 19.8 months. Tx would be greater. The pub selected historical 12.7 months as control SOC. Bosch seems to have selected 14.7 months. Either way, the results are impressive. Classical may account for about 20% to 25%(maybe even up to 30%) of all stage IV glios and neural less than 15%. So mesenchymal could well be performing extremely well but the blended OS of 19.8 months would reflect the lesser affected Classical and Neural strains, thus bringing down the blended figure. Non-the-less, it is still quite impressive.
Tha anomaly is M+ with pro-neural. Here it appears, depending upon where you place the control stake(the pub selected historical 21.7 months but it has gone up as high as 34 months--although a small study and thus likely to be an outlier), that the vaccine works even better although Liau and Prins found that the vaccine had little to no effect on pro neural. I think that was a rather general statement and it would depend upon G-Cimp status. However, and still, the vast majority of pro-neural would not be affected by the vaccine. However, the pub shows quite the opposite of LL and RP's clinical findings in that the vaccine works even better on M- which seems to be predominantly populated by pro-neural, which constitutes about 15% of the stage IV glio population. It would be very interesting to pose this anomaly to LL and RP and get their take on it. Bosch has only commented upon the M+/M- categorisations but has not waded into the mesenchymal and pro-neural weeds. However, all of the foregoing analysis seems to point to the hypothesis that the vaccine works across all groupings to a greater or lesser extent. Even Bosch commented that the vaccine appears to work regardless of whether M+ or M-. JMHO.
AI
