ADAPTIVE AND INNATE IMMUNE RESPONSES
TRIGGERED TO NEUTRALIZE GASTRIN HORMONES
AS A THERAPY FOR GI CANCERS



TYG300
Target: CCK2 receptor

MODE OF ACTION
After subcutaneous or intramuscular application, the drug, through its warhead, docks specifically onto local CD32a (FcgammaRIIa)  expressing cells such as monocytes and monocyte-derived dendritic cells (mDCs) as well as plasmacytoid dendritic cells (pDCs). In addition the ACI is recognized by immunogen specific B cells (figure/step1). This triggers a cascade of anti tumour specific events:

Stacks Image 53
Phase one: ARMING:
Step 1a: ACI is recognized by auto-antigen specific B cell and binds to CD32b (with low affinity) and auto-antigen specific B cell receptor (with low affinity) -> increased avidity -> stable binding of ACI
Step 1b: ACI binds stably to CD32 (high affinity) on pDCs
Step 2: ACI is actively internalized by B cells and pDCs
Step 3a: TLR9 is triggered and will change anergic B cells into reactive B cells, who will present auto-antigen Th cell epitopes on HLA class II molecules
Step 3b: TLR9 is triggered while pDCs present autoantigen T cell epitopes on HLA class I and II molecules to anergic Tc cells and Th cells respectively (cross presentation) -> induction of reactive Th and Tc cells
Step 4a: Reactive Th cells provide help for auto-reactive B cells -> IgG anti autoantigen production
Step 4b: Reactive Th cells provide help for auto-reactive Tc cells -> activated Tc cells induction

Phase two: 4-fold KILLING:
Step 5a1: IgG molecules bind to target (growth hormone) leading to tumour starvation
Step 5a2,3: IgG molecules bind to target and mediate CDC or ADCC
Step 5b: Activated Tc cells recognize tumour cell and kill the target.

[Sleeker_special_clear]