NorthWest Biotherapeutics Inc (NWBO)

[Smokey21]

Flipper, that Patent document is a treasure trove of information about DCVAX (both L and Direct), although it is focused on DIRECT. There are many hidden nuggets in it. To me, this paragraph is the holy grail of why it works so well and can even be tuned to be better in future iterations:

Fully mature dendritic cells are not preferred for the present methods and compositions because once they are fully mature the cells no longer efficiently process antigen. Further, immature dendritic cells as used in prior methods which have not been induced to begin maturation are not desired because the immunosuppressive environment typically found within a tumor, or in the tissue surrounding a tumor, include substantial concentrations of cytokines known to prevent the processing of antigen by immature dendritic cells. In the present disclosure, partial maturation and optimal activation of the immature dendritic cells down regulates cytokine receptors on the surface of the cell rendering them less sensitive or responsive to any immunosuppressive effects of cytokines present in the intratumoral space, or surrounding tissue, and provides for cells that can efficiently uptake and process antigens present within the intratumoral space or surrounding tissue. The dendritic cells take up and process substantial amounts of tumor antigen from apoptotic and dying tumor cells found within the intratumoral space or in the surrounding tissue. Once the administered partially matured and optimally activated dendritic cells have effectively matured within the intratumoral space as measured by, for example, the expression of the chemokine receptor CCR7, the dendritic cells migrate to the lymph nodes where the dendritic cells now presenting antigen will contact T cells, particularly naive T cells, to up regulate the immune response to any tumor antigens presented by the dendritic cells.