NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Here is something else I wrote about DCVax-l therapy in cases where 5-ala surgery is/was used.

Monday, 10/14/19 09:00:48 AM
Re: None 0
Post # of 342471
My understanding is that PDD uses blue light at 417 nanometers (wavelength) to trigger 5-ala fluorescence.

My further understanding that this range (close enough at 405 nanometers) can also cause aptosis of some cancer cells on the surface of tumors (aka: PDT) plus increase the immunogenicity of other cancer cells on the surface of the tumor.

My understanding is that tumors resected using 5-ala likely increase in DAMPS (aka: danger signaling molecules) and more immunogenic properties on average, plus the lysate may or may not include debris from tumors that terminated by aptosis.

My hypothesis is that resected tumors with 5-ala are more immonognic and provide danger signaling molecules when combined as a lysate with DCVax-L. DCVax-L DCs are also stimulated by lysate from the freeze thaw process which increases damps. Just to be clear, in Europe, essentially DCVax-L gets the benefit of tumor lysate that was previously optimized by 5-ala resection plus freeze thaw processing.

My running hypothesis is that the increased percentage of total resection also exhibited in most 5-ala resections is synergistic with DCVax-L, because it:

1. Decreasess the tumor's local and systemic immunosuppressive capabilities -- thus allowing DCVax-l a better chance to get a foothold.
2. Increases the amount of tumor lysate available to make a more complete array of antigens for lysate production and eventual DC stimulation.

My hypothesis is that, for all these reasons, DCVax-L worked so well in Europe, on average, when 5-ala resection became part of the equation, that adding more people to control would have one to possibly three deleterious consequences:

1. It might be unethical, because control patients would not have this optimal cancer treatment.
2. It might cause more extreme pseudoprogression, which, at the time, was harder to differentiate. This was a concern for the trial endpoints.
3. The European protocol, utilizing 5-ala, might make crossover from placebo more responsive, and thus lose the OS curve separation necessary for the antiquated endpoints.

Solution? Stop placing people in Europe into the control arm.

If this is what happened, my guess is that it's all very clear to the company and agencies behind the curtain.

(Note: The U.S.A. is now starting to adopt 5-ala (which was approved here in 2017) as a good way for surgeons to obtain more complete resections.)