Why Conventional Solid Tumor Targeting CAR-T Cells Do Not Work
Why Conventional Solid Tumor Targeting CAR-T Cells Do Not Work
How chimeric antigen receptor modified T cells (CAR-T cells) were designed to work:
- Chimeric antigen receptor modified T cells (CAR-T cells) were designed to bind the cancer antigen and become activated (by intracellular costimulatory and CD3 zeta signaling), which causes proliferation of the CAR-T cells and killing of the cancer cells.
Why CD19 CART cells work well to treat ALL and NHL:
- With easy access to the blood cancer cells, the CD19 CAR-T cells efficiently kill the cancer cells and proliferate potentially more than 1000-fold.
- Proliferation is positively correlated and essential for efficacy.
Why conventional solid tumor targeting CART cells do not work:
- Solid tumor targeting CAR-T cells do NOT currently work because the solid tumor target antigen is NOT in the blood stream with the CAR-T cells (antigens are localized inside the tumor), so CAR-T cells do NOT activate or proliferate.
- Without proliferation there are relatively few solid tumor CAR-T cells in circulation after infusion, the CAR-T cells will be at least 100X below the effective cell numbers found in blood cancer CAR-T therapy.
CoupledCAR Platform Technology
What is CoupledCAR Technology?
Chimeric antigen receptor modified T cells (CAR-T cells) were designed to bind the cancer antigen and become activated (by intracellular costimulatory and CD3 zeta signaling), which causes proliferation of the CAR-T cells and killing of the cancer cells.
CoupledCAR-T cells are engineered to release cytokines that promote solid tumor CAR-T cell proliferation, infiltration of the tumor and killing of target cells.
The origin of CoupledCAR is the observation that CD19 CAR-T Cell activity triggers the immune system and results in proliferation of all T cells, including any non-transduced T cells, which suggests that CD19 CAR-T cell activity can induce proliferation of solid tumor CAR-T cells without the need for the solid tumor CAR-T cells to bind target antigen.
CoupledCAR Mechanism of Action:
As CD19 CAR-T cells kill B cells, signaling molecules are generated (A), that result in activation and proliferation of the solid tumor targeted CAR-T cells without engagement of solid tumor antigen (B)
CoupledCAR-T cells release cytokines that promote solid tumor CAR-T cell infiltration of the tumor (C) and killing of target cells (D)
