Replies to post #249040 on NorthWest Biotherapeutics Inc (NWBO)

[Evaluate]

You wrote: “Dendritic Cells which were young and powerful”

I believe Marnix Bosch has made it a point that they have figured out that the dendritic cells need to be “partially matured” (not young, not mature, but in between).

After generating DCs, the cells are pulsed with an antigen and injected back into the patient.
The choice and source of the antigen (e.g., purified protein or cell lysate), as well as the loading method, have a large effect on outcome and vary widely between studies.
Another consideration in DC-based immunotherapy is DC maturation. Immature DCs take up antigens more readily; however, they also induce T-cell tolerance by triggering apoptosis, promoting anergy, or priming regulatory T cell (Treg) differenti- ation in T cells.
To ensure that the exogenously loaded DCs will elicit an active immune response, maturation agents must be used during vaccine preparation, either before or after antigen loading.
Maturation agents include Toll-like receptor (TLR) agonists or mixtures of cytokines, such as tumor necrosis factor a (TNFa), interleukin (IL)-1b, IL6, and prostaglandin E2 (PGE2; ref. 10).
Differentiation protocols often include IL4 to inhibit differentiation into macrophages instead of DCs, but this is not required if monocyte activation is avoided during purification.
Some strategies supplement their maturation compounds with interferon g (IFNg), IFNa, and polyinosinic: polycytidylic acid to generate mature type-1–polarized DCs that secrete IL12. The mature DCs induce a T-helper cell 1 (TH1)-type profile that elicits natural killer cell and CTL activation. CTL activation triggers a proinflammatory state, stimulating these cells to kill tumor cells directly.

https://clincancerres.aacrjournals.org/content/clincanres/early/2018/06/18/1078-0432.CCR-17-2707.full.pdf