NorthWest Biotherapeutics Inc (NWBO)

[MolBiol]

Hi Long,

Sorry but I hve to be brief here. I'm in the middle of something at work that I can't be away from for long (no pun intended). I'll try ot get back to you with a more elaborate response if needed later when I have more time.

Basically, cells differentiate into DCs from a progenitor cell (myeloid lineage). I'm thinking that other immune cells can differentiate into DCs but I would need to look into that. Therefore, DCs aren't multiplied exactly, but rather are the products of a progenitor cell that differentiates into the DC. This is where the leukopheresis comes in to provide the mo/mx cells for this purpose.

As for the BCG, my understanding of its use is simply as adjuvant (in vitro). Since the tumor lysate is likely comprised of only self antigens, their will be nothing to bind to the pattern recognition receptors (PRRs). Self antigens don't have pathogen-associated molecular patterns (PAMPS). The BCG should, although I don't know that for certain. lipopolysaccharide (LPS) is a more common PRR activator. I think the BCG is present in combination with IFN-gamma to activate an arm of the pathogen response in DCs that will lead to lots of MHC:antigen complexes on the surface and also the co-stimulatory molecules needed to produce TH1 and CTLs.

Sorry so brief without more specific references....