Replies to post #222745 on NorthWest Biotherapeutics Inc (NWBO)

[Smokey21]

Nice Try Ex, but you are the one distorting things. This is pulled directly from the report:

In May of 2018, Liau et al. published interim results on the first Phase III clinical trial of autologous tumor lysate pulsed dendritic cell vaccine (DCVax-L) in newly diagnosed GBM. Patients underwent standard surgery and chemoradiation, after which they were randomized 2:1 to receive either temozolomide plus DCVax-L or temozolomide and placebo. Following recurrence, patients were given the option of receiving DCVax-L; therefore, >90% of patients with the intent to treat population received DCVax-L. The median survival for the intent to treat population was 23.1 months from surgery with 223 patients who are >30 months past surgery and 182 patients who are >62 months past surgery. Only 21% of patients had grade 3 or 4 adverse events. The results of this Phase III clinical trial show promising feasibility of integrating DCV into standard therapy and suggests a survival benefit [214].

Yours is the summary conclusion of the report, which is speaking of DC vaccines in general.

[biosectinvestor]

That’s as strong as anything gets at this stage. For THAT to be their conclusion is pretty encouraging. OF COURSE it is not conclusively. We don’t have the final results.

However, they also clearly reference the interim results for their inference, cautioning that they anxiously wait for validation with final results...

Only the pessimists could take such encouraging analysis and turn it into something less than... a glass half empty...

[CherryTree1]

What you said is not quite true either ex.
Marzan stated:

Johns Hopkins endorses DcVax L as SOC is huge.

If you read the article that they are talking role of DC Vaccines in the current standard of care. Here is a relevant except:

5.4. Role of DC Vaccines in Current Standard of Care
As we await the results of these trials, considerations into where DCVs fit into the current standard of care should be evaluated. There is no clear consensus on whether DCVs should be administered before maximal resection, concurrently with temozolomide, after radiation therapy, or any other variations. Each method has pros and cons that ultimately require the use of clinical studies to gain further insight. Historically, novel therapies such as DCVs have been given in the recurrent setting after standard of care consisting of surgical resection followed by adjuvant temozolomide and radiation. While the administration of DCVs after maximal surgical resection is typically advocated due to the idea that decreased tumor burden leads to a decrease in tumor-associated immune suppression and stronger cytotoxic immune response, the timing of DCVs in conjunction with or after adjuvant chemoradiation is less clear [218].

https://www.mdpi.com/2072-6694/11/4/537/htm

[longfellow95]

Seeing as InmuneBio is ringing bells at the moment, I thought this extract from Hope's link was particularly interesting:-

One adjuvant that has shown promise in preclinical studies is the use of natural killer T (NKT) cells. NKT cells display several desirable anti-tumor properties due to their ability to directly lyse tumor cells. These cells secrete both TH1 and TH2 cytokines that can modulate T cell activity and promote DC maturation through CD40L/CD40-mediated interactions [151,152,153]. Although direct anti-tumor lysis mediated by NK cells has been reported to be restricted to tumor cells that display CD1d protein on their surface [154], malignant gliomas have been shown to express CD1d. Another advantage of NKT cells is their anti-tumor immunomodulatory effect on the GBM TME. These effects range from activating immune cells such as B cells, T cells, and DCs to downregulating and killing pro-tumor TAMs and MDSCs [147,155,156,157]. Furthermore, the synergistic interaction between NKT cells and DCs leads to enhanced CD4+ and CD8+ T cell activation and has been efficacious in inducing strong and long-lasting immune responses [155,158,159,160]. In one study, the authors pulsed DCs with alpha-galactosylceramide, an NKT cell activator, and the DCs were then co-cultured with NKT cells isolated from glioma patients. The NKT cells showed robust expansion ability and functionality with a significant increase in the secretion of IFN-?. Furthermore, the expanded NKT cells demonstrated significant cytotoxic activity ex vivo against U251 glioma cells, a CD1d expressing cell line, in a Cr51 release assay compared to A172 glioma cells, a CD1d negative cell line [161]. Liu et al. also highlighted NKT cell’s efficacy as a DCV adjuvant against gliomas by using DCs pulsed with glioma-derived exosomes and a-galactosylceramide in orthotopically implanted C6 GBM cells. The authors showed an increased survival response compared to DCs pulsed with tumor lysate or with a-galactosylceramide only [147]. Thus, by optimizing the pulsed antigen for the DCs through the use of glioma-derived exosomes instead of whole tumor-lysate and the addition of an adjuvant in the form of NKT cells, Liu et al. demonstrated that combinatorial therapy can lead to synergistic cytotoxic anti-tumor activity against gliomas.

https://www.mdpi.com/2072-6694/11/4/537/htm

[GoodGuyBill]

Ex, You just did the very thing you accused Marzan is doing. The following quotes does "suggest" anything. It states it clearly:

The results of this Phase III clinical trial show promising feasibility of integrating DCV into standard therapy and suggests a survival benefit [214].

Shame!

[biosectinvestor]

“The results of this Phase III clinical trial show promising feasibility of integrating DCV into standard therapy and suggests a survival benefit [214].”