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Re: CogDiss 1188X post# 207619

Wednesday, 01/09/2019 7:36:28 PM

Wednesday, January 09, 2019 7:36:28 PM

Post# of 700696

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.

:)
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