NorthWest Biotherapeutics Inc (NWBO)

[Doc logic]

skitahoe,

The observations made about Direct are with it being tested in a very suboptimal manner. Until a tumor environment immune response is controlled by properly activated DCs, the immune system shut down response from inflammation caused by an initial immune response from treatment will create the need for anti PD-1 or anti PDL-1 adjuvant therapy. Once proper signaling from Direct or uninhibited and properly activated native DCs get established in the tumor microenvironment and are maintained there by proper cycling of native DCs and enough exposed cancer antigen targets or treatment spacing of Direct the need for other therapies no longer exists. The action becomes like a normal immune response by the body to any other common disease. Methylated tumors are more susceptible but CSF1-R targeting treatments allow for even unmethylated status to become susceptible.
Generally speaking the tumor microenvironment prevents native DC response from being sufficient as those DCs become compromised by cancer cell signaling interference and the normal cells they often hide behind. Some types of viral infections have at times created a situation where cancer cells can become exposed in the cancer’s attempt to fight off the invader and native DCs have been able to identify the cancer, attack it and in some cases eliminate it. That is why Coley’s toxins worked at times over 100 years ago and also how viral vectors are often used to activate immune response against cancer in trials today that are utilizing them for such purpose. Best wishes.