Replies to post #736455 on NorthWest Biotherapeutics Inc (NWBO)

[Hopeforthefuture3]

Survivor, Dr's. Liau and Prins have said for many years the mesenchymal group has the greatest % of responders to immunotherapy (dcvax) because they are the most immunogenic - greatest about of mutations to be potentially targeted and why some other subgroups with less mutations do not seem to respond as well. Prins has a good presentation on this from 2016 and published in 2011. In a Liau presentation from 2023 she again says the same thing

[Hopeforthefuture3]

survivor, here is some additional detail from the original paper:

https://pmc.ncbi.nlm.nih.gov/articles/PMC3071163/

As shown in Figure 4, patients enrolled on our trial with the proneural gene expression signature had an overall survival that was indistinguishable from a set of 60 contemporary proneural tumors analyzed from UCLA and three other institutions (21) (p=0.664; Fig. 4A). In contrast to this, patients in our DC vaccine trial with mesenchymal gene expression signatures had a significantly extended survival compared with 82 concurrently collected tumors that were found to have these same gene expression signatures (p=0.0046; Fig. 4B). While these data are not intended to represent efficacy, such information is noteworthy because glioblastoma patients with mesenchymal gene expression patterns typically have the worst prognosis and are the most refractory to current therapies

Since the mesenchymal expression signature includes numerous genes associated with inflammation, and tumor-specific T cells are known to be attracted to pro-inflammatory signals, we evaluated whether patients on our DC trial with mesenchymal gene expression signatures also had increased tumor infiltrating lymphocytes (TILs). As shown in Figure 5, tumors with a mesenchymal gene expression signature had significantly increased CD3+ and CD8+ TILs compared with PN tumors (p=0.006)

If patients did not develop any toxic side effects from the experimental treatment and had stable disease for over three months, they received booster injections at the same dosage of tumor lysate-pulsed DC concurrently with either 5% imiquimod cream (Aldara™, a TLR-7 agonist) or poly-ICLC (Hiltonol™, a TLR-3 agonist). Due to initial safety/toxicity concerns of experimental allergic encephalomyelitis (EAE) (18) resulting from the combined use of DC vaccination and TLR agonists, these immune response modifiers were used only in the booster phase of the protocol, after patients had shown acceptable toxicity profiles to DC-lysate vaccinations alone.
Sorry - can't get the Figure pasted in use the link to see the figure
Figure 4.

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Extended survival in DC vaccinated patients with mesenchymal gene expression signatures, but not in patients with a proneural signature. The overall survival time of DC vaccine patients expressing a (A) Proneural (PN) gene signature (n=5) or (B) Mesenchymal (Mes) gene signature (n=9) was compared with the survival generated from a control, multi-institutional dataset of PN (n=60) or Mes glioblastomas (n=82; solid lines) previously published by our group (21). To accurately account for the potential bias associated with the time delay needed to generate the DC vaccine, we omitted control patients that experienced early progression (<250 days). PN comparison: p=0.664 (not statistically different, ns); Mes comparison (p=0.0046) by the Log-rank (Mantel-Cox) Test calculated in GraphPad software.

[iclight]

Try reading my whole post and responding the specifics.

The sickest of the total GBM population, which you people keep quoting in the 5% 5 year survival includes all those who failed the inclusion/exclusion criteria.

A patient with biopsy only and not near total GTR is sicker than the patient with total or near total GTR. And they weren't included in the trial. This trial limited participants to under 70 years of age. 25% of GBM patients are diagnosed over 70. You see those "disease progression", "general in/exclusion/history criteria", "clinical deterioration", and "surgery not done or processed" exclusions? Those people are sicker than the ones who made the trial.



Since you don't understand basic inclusion/exclusion criteria at this point in your financial gamble there is no point in arguing with you. Hell, where is all the control arm data? They won't release it.

Where is the comparison of ALL mesenchymal patients in the trial comparing the trial control arm to the trial treatment arm?