NorthWest Biotherapeutics Inc (NWBO)

[Doc logic]

sentiment stocks,

There are some very interesting ideas that have come to mind for me over the course of my research into dendritic cell function with regard to the entire immune response. I believe that one of their functions may be missing or limited when DCVax-L is given initially which may be something that NWBO figured out was a necessary component of a more complete immune response. You see, normal circulatory DCs are designed to move towards areas of inflamation in the body as the initial responder. Once at an inflamatory signal site they can assess the situation with the specific assay of signalling and environmental conditions that they encounter there and begin additional signalling themselves. In this process they are normally able to regulate macrophage activity and function to some degree. Cancer cells also have the ability to affect function of macrophages. If these sentry type DCs do not have the capacity to induce proper signalling at the site of inflamation (unprimed or improperly primed circulatory DCs) due to confounded signalling caused by cancer or leave the area of inflamation too soon due to genetic changes from environmental conditions, their influence is lost. Their antigen presenting function on its own also loses meaning as Tregs maintain or regain control. DCVax-L skips around this initial scout stage by injecting primed and matured DCs into lymph rich areas away from the hijacked tumor draining lymph zones which then activates and perhaps reactivates the T-cell response. Direct essentially has the ability to overcome this lost step by having DCs being placed directly into the tumor environment so the scout signalling step is not lost. While priming of the entire immune system with a tetanus vaccine before treatment or using viral vectors along with treatments to essentially prime the cancer environment to drop it's guard show promise, getting primed DCs to stay long enough or renewed often enough for a cascade effect to develop seems to be the ideally safe way to overcome the tumor environment. The other option is to have alternating inhibitor treatment to extend the length of time that educated killer T-cells can remain unhindered.

I have seen the comments by researchers made about the mouse study which seem to indicate that checkpoint inhibitor build is relatively quick which would lead one to believe that this is an inevitable consequence of DC therapy. The way the comments are written also lends credence to this idea. I still wonder if the DCs utilized in the mouse study are influenced by the more rapid metabolism of mice and move out of the cancer zone more quickly than in a human host which would lead to this aforementioned conclusion. In other words one might ask whether or not more frequent dosing alone might be enough to overcome immunosuppressive responses. This would be a good question for the scientific advisory board to look into if it has not already been satisfactorily answered by data. Best wishes.