HI Abets:
The chart is excellent. For now nothing to add, modify or delete. Your chart summarizes extremely well.
As you will note, the issue is about MOA and pathways in which DCVAX works. Although glioblastoma stage IV is a generic nomenclature, the subclasses of MES, pro neural, classical and neural therein are different cancers. Why is DC VAX seemingly so effective in M+ but overall not so in M-. Is it due in great measure to the immunogenosity of the cancer? In the case of MES, it would seem so as found by LL and Prins. But not generally in pro neural although there is at least one sub class of pro neural where it is relatively effective. I recall that there was a comparison made with CLDX on classical(HLA-1 and 2, EGFRviii) where DC Vax was just as effective if not more than the single agent approach due to heterogeneity.
Doc Logic from his own research indicates that DC VAX is effective in a very small MES methylated group. From the chart that I have referenced in our discussions, this seems valid because the methylated group as a whole did significantly better--on a blended basis--than the non methylated group of which MES is a part. However, while I have no reason to doubt Doc Logic's research, I have explained why I believe that LL/RP were referring to the larger MES group due to the different pathway available as a result of the immunogeneity of MES as a whole. It may well be that it is even more effective in the methylated group because in addition to immunogeneity you have an inhibition of the cellular repair mechanism. The reason that M-, as a whole did not perform better may have been due to the counterbalancing classical and neural groups that may respond significantly less than unmethylated MES and which, accordingly, brought down the performance of the M- group as a whole. I believe that LL/RP were excited because the vaccine worked very well on a significantly large MES subgroup rather than just upon a relatively de minimis subgroup. Again, I am no expert. Trying to understand this better and throwing out thought experiments that others more knowledgeable can consider and correct. My own understanding improves and I can then feel either more or less comfortable with my investment depending upon the various viewpoints--or then again, not at all. Hope I have not confused you but JMHO.
Best,
Um
