Hyperopia:
Thank you very much for bringing this abstract to my attention. In my view, this commentary and landscape review of EMT/PMT transformations is extremely important and bodes very well for highly positive results in our trial. While the various details involving these transformations are extremely varied and complex, bottom line, they demonstrate the plasticity and heterogeneity of both nGBM and rGBM.
In this regard, it appears rather well established that to a large extent, proneural subtypes transform ultimately into MES phenotypes. In addition, in this particular study, the composition of the various GBM molecular subtypes appear to be significantly different from those which I provided in my previous post which may signal even better trial results and may indeed be a major reason as to why the SAB has advised to keep the trial going for so long. This study also suggests a viable strategy for improving treatment modalities wrt DCVAX L administration. Whilst this abstract is a very scholarly article, it is a little surprising that DCVAX L was not mentioned and yet bevacizumab was even though it has been shown to be a failed therapy due to treatment resistance in connection with angio-genesis(GBM tumors have high vascularity).
The composition of GBM molecular subtypes are as follows:
1. MES is 39%;
2. Classical is 36%; and,
3. PN is 25%.
By and large the study suggests that ultimately, PN transforms into the MES signature, due to a number of factors including the effects of SOC treatment in both nGBM and rGBM. The PN percentage component in this review is quite high at 25%. In addition, there is a sub-category of PN which is negative G-Cimp/IDHwt, but very small, that exhibits an MES like signature and accordingly may be more susceptible to DCVAX L efficacy. Accordingly, the patient population covered by DCVAX L efficacy may constitute an extremely large percentage of the population if you let the trial run long enough to permit rather whole sale PMT. In addition, there is EMT, although to a lesser extent, as well as classical with the IDHwt signature and one can now understand why Dr. Ashkans has emphatically stated that the vaccine can help everybody in varying degrees and, seemingly, the entire spectrum is covered. Treatment effect is an important MES inducer where previous clinical trials have found that DCVAX is especially efficacious for that molecular subtype. Accordingly, trial results may indeed show even better results due to the length of the trial and the tendency for EMT/PMT transformations. Furthermore, this study appears to support the notion that if NWBO receives regulatory approval, it will be broad and likely include rGBM. JMHO.
This article is exciting news!
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