Replies to post #395707 on NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

Direct is only partially matured. It is not exposed to any tumor antigen. The MOA will supposedly be to go into the tumor site and mature in-vivo.

-L is full matured in the presence of the full tumor lysate.

That is a huge difference.

[HappyLibrarian]

L and Direct are different in that Direct is more versatile and advanced. When you reflect on how awesome Direct could be you get mad that L stalling out is setting it back years if not half a decade.

The biggest difference is that Direct does not require surgery first but can be injected into inoperable tumors and handle the differences between different tumors in the same body.

L is great in its own right but it is more expensive to do abs is twenty year plus old technology we need to start bringing money with to be able to afford get Direct moving.

[exwannabe]

Let me try again with a more complete answer.

The final step in the full maturation of the DC is the activation where they have been exposed to the antigen. Once activated, they will return home in order to transfer the antigen to T cells so they can attack the source.

With Direct, this last step has to take place in the tumor micro-enviroment which has many factors that make the process of recognizing the antigens difficult. Prins gave a good speech on this a while back if you recall.

Even if Direct was 100% identical to -L prior to activation, there is no reason to assume they would be able to recognize and activate in the actual tumor site as they can in a test tube.

[pqr]

hyper- again most excellent rebuttal. I don’t mean to suggest that I understood your entire rebuttal. But I understood ex’s point AND I understood that ex had no satisfactory answer to your question

For me … breadcrumbs.

[longfellow95]

Have a look at this, hyperopia.

https://clincancerres.aacrjournals.org/content/clincanres/24/16/3845.full.pdf

It's probably the best available description of Direct methodology.
There are many differences between the production of Direct and the production of L and how each is administered. Differences include (but aren't limited to) degree of DC maturation, the differences in the constituents of the maturational cocktail and at what point in the process these agents are employed, site of injection, and site of antigen presentation. And a lot of the processes are proprietary anyway.
I certainly don't profess to have anything other than a very rudimentary understanding of the critical processes that are involved, and how precisely these processes differ between the two products.

Dr Bosch is probably the only individual that could give an in-depth description of the differences and similarities, and which distinctions are considered critical to the optimal efficacy of each.
We know that for Direct, Method B was considered a critical enhancement, using a different time frame to optimize the required partial DC maturation.

So, they are similar in terms of broad principles and mechanism of action, but considerably different in terms of precise detailed preparation and administration. And you could say that makes for very different products. The process is the product!

I'm sure they learned a lot from the PI, which they will employ in the P2's. Method B obviously, but other refinements including ensuring they isolate the highest functional DC precursors to start with. Plus, as we know, the injection of multiple tumors where indicated.