Therapeutic Principle

The immune system has four natural killing mechanisms to defeat cancer cells:

1. Growth factor starvation, i.e. preventing tumor proliferation
2. Complement Dependent Cytotoxicity (CDC), the process whereby tumour specific IgG antibodies activate the classical complement system killing cancer cells by damaging their cell membranes.
3. Antibody Dependent Cellular Cytotoxicity (ADCC), a mechanism whereby tumour specific IgG antibodies activate Natural Killers (NK) cells, which selectively kill the cancer cells
4. Tumour specific Cytotoxic T cells (Tc) cells. This type of white blood cell kills cancer cells, by recognizing small parts of tumour specific or tumour associated proteins. Tc’s are also very effective in killing virus infected cells.

OncoQR ML´s Active Checkpoint Control Immunotherapy mobilizes all four naturally available tumor killing mechanisms of the immune system. It does so selectively, i.e. as a “targeted and specific weapon” it only activates the killing mechanism(s) required for defeating a specific disease or cancer target, there is no risk for overreactions of the immune system that are usually the cause major side effects in other treatments. 

PHASE 1: Arming the Immune Cells against Cancer Cells

• 1a: ACCI 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 ACCI
• 1b: ACCI binds stably to CD32a (high affinity) on pDCs
• 2: ACCI is actively internalized by B cells and pDCs
• 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
• 3b: TLR9 is triggered and activated pDCs present autoantigen T cell epitopes on HLA class I and II molecules to anergic Tc cells (cross presentation) and Th cells respectively  -> induction of reactive Th cells and Tc cells
• 4a: Reactive Th cells provide help for auto-reactive B cells ->IgG anti autoantigen production
• 4b: Reactive Th cells provide help for auto-reactive Tc cells -> activated Tc cells Induction

PHASE 2: Activated Immune Cells kill Cancer Cells

• 5a / 1: IgG molecules bind to their target (growth hormone), leading to tumor starvation
• 5a / 2 IgG molecules bind to their target and mediate CDC
• 5a / 3 IgG molecules bind to their target and mediate ADCC
• 5b: Activated Tc cells recognize the tumor cell and kill it