What the JTM journal article(and SNO update) suggests is that both non-methylated and methylated groups are efficaciously treated by DC VAX L when looking at blinded data as compared to historical SOC. The delta for non-methylated is about 7 months and the delta for methylated is about 14 months. Treatment arm deltas are most probably even longer. Drs. Liau and Prins concluded from their earlier trials that the vaccine was especially efficacious for MES as a whole. They did not break down MES methylated and MES non-methylated. However, they did find that MES, as a whole, is immunogenic. Accordingly, this would suggest that the vaccine is especially efficacious wrt to methylated MES due to impaired cellular repair mechanism, higher thresholds of T cells and less immunosuppressive micr-tumour environment. In other words, the morphology of this particular molecular sub-group is particularly susceptible to the vaccine as an adjuvant to current SOC. The non-methylated MES sub-group is also efficaciously treated, even though it lacks methylation, due to its immunogenicity. I believe, although i am not sure, that methylated MES sub-group makes up a significant proportion of the larger Methylated grouping but not 100%. There are other methylated variants. In the trial, the identified methylated group makes up about 44% of the total M+/M- major groupings. In the non-methylated group I believe there is an non-methylate MES sub-group that makes up a significant proportion of the total non-methylated group. MES, as a whole, makes up a rather significant proportion of nGBM ranging anywhere between 25%~48% depending upon the literature read. Accordingly, as was suggested by Dr. Prins, there was little to no effect by the vaccine on the overall pro-neural sub-molecular group and perhaps some efficacy in other groups,i.e., classical and neural. Assuming that these less affected sub-molecular groups were a part of the un-methylated group, they may have likely masked the significant efficacious effect of the vaccine upon non-methylated MES. Despite that, the delta was still 7 months in this group, suggesting a significantly longer Tx OS for non-methylated MES. Hence, trial results may indeed show that the vaccine is efficacious to some extent extent across all sub-molecular groups especially in the methylated group but not so much in the non-methylated group except wrt MES. Since MES takes up a significant proportion of nGBM and there are a smattering of other sub-molecular groups especially in methylated, the efficaciousness of the vaccine may be especially pervasive in 50% or more of nGBM. Pro-neural tends to morph into MES and it is estimated that upon recurrence 85% of rGBM is composed of MES. Accordingly, the vaccine does indeed work, to a greater or lesser extent, on all sub-molecular groups depending upon their morphology and evolvement through mutation.The vaccine may be efficacious for both nGBM and rGBM which is even a larger market with a really significant proportion of MES where the vaccine is especially effective. JMHO.
