There are generally considered to be three broad phenotypes of immune-resistant tumours:
Type I: Immune Desert
In this phenotype there are very few imune cells evident within the tumour mass. It could be that the cells were not generated or were deleted during activation. The immune system naturally deletes activated T-cells during late stages of the adaptive immune response when antigens persist. Clearly an established tumour represents a case of persistent antigens and this deletion mechanism, via a process known as Activation-Induced Cell Death (AICD), may be an important element of tumour immune resistance.
Another potential cause of the dearth of immune cells is failed extravasation from the bloodstream. Tumour endothelium can either prevent cells passing though or induce cellular death during adhesion and extravasation.
Type II: Immune Excluded
In these tumours immune cells have accumulated in the tumour stroma but few are seen within the tumour parenchyma where they need to be to kill the cancer cells themselves. Tumours can hijack immune control mechanisms, such as AICD, to attack infiltrating immune cells and delete them, preventing their accumulation within the tumour cell mass.
Type III: Inflamed
In this situation there appears to be adequate accumulation of immune cells within the tumour parenchyma but immune attack is still ineffective. These cells may have been shunted into an "exhausted" state by the tumour microenvironment or may be apoptotic and on their way to cell death, Again these mechanisms may be the result of cancer cells hijacking immune regulatory molecules ( including immune checkpoints). The presence within the tumour of immune inhibitory cells such as regulatory T cells and monocyte derived suppressor cells can severely impede cancer cell killing.
Fast Biopharma addresses targets that can be invloved in all three types of tumour immune resistance.
FBP002 is our lead therapeutic candidate. It is a potent humanised antibody against a key regulator of the immune response. Blocking this target has antitumour effects through mechanisms including increasing tumour-infiltrating effector cells and decreasing tumour Tregs. Studies strongly suggest that this treatment will be complementary to current immuno-oncology therapies.
FBP002 is active in a range of immuno-stimulatory assays and has good manufacturability. Preclinical studies are ongoing.