Replies to post #207619 on NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

The antigens tested for in the study aren’t neoantigen, but are instead known tumor associated antigens. Is the assertion that DCs can’t identify neoantigens? Very unlikely since that’s its job, correct?

I am by no means an expert on the nitty gritty of the science, but would add this to the conversation.

L is made from the tumor and of course, the leukepheresis material. For the P3 trial, they use the newly diagnosed tumor - so basically, the first or initial tumor. I think from that tumor material there are likely less neoantigens present because as I understand it, those develop later, as the tumor mutates. The antigens become less and less like self in the next generation tumors, and what develops instead are the neoantigens.

So... for some of the patients, L might work really well on the first tumors, especially if their type of GBM is more mutated, because there are more targets for the T Cells to chase after. I think that's why immunotherapy worked so well for melanoma - it was highly mutated. But for those who's GBM is less mutated, initially anyway, Prins' thinking was that by adding a CI to the treatment, they could better effect a result.

Now when it comes to Direct, it's injected directly into the tumor, which is how it obtains the antigens it tells the immune system to target. Well, most of those tumors have mutated from the original, so there are likely many neoantigens present on those tumors. So IMO, Direct is more likely to act as a neoantigent vaccine as it picks up whatever the targets are on the tumor, including whatever neoantigens are present, and takes all that to the command center.

I suppose if L were mixed with a recurrent GBM tumor, it would then contain more neoantigens as that would be a tumor that had mutated from the original one. That's how I understand it anyway.

Of course, anyone who understands the MOA better is welcome to correct me or explain it more comprehensively than I have here.

:)

[jammyjames]

Hi cog. Sorry i was on holiday so hadn´t got round to responding. Good effort trying to dig up some evidence.

Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma.

Unfortunately there appears to be no negative control in this study so i´d take the results with a pinch of salt (they internally controlled with the same patients pre and post vaccination). By that i mean they didn´t test whether there´s an expansion of CTLs that are specific to non-tumour associated antigens. i.e it might be a general rather than specific effect - for all we know there's an expansion of CTLs targeting Actin!

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

Cytokine responsiveness of CD8+ T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients

These two papers do not address neoantigens.

Overall as i mentioned before this has no bearing on whether DCVax-L works or not, simply I still haven't seen any strong evidence that the DCVax-L MOA (assuming it has some action) is by directing the immune system to neoantigens.