Universal
Switchable CAR
Universal
Switchable CAR
AvenCell is developing a proprietary universal switchable CAR-T platform to improve the therapeutic window and increase the efficacy and safety of CAR-T cell therapies especially against less differentially expressed antigens such as CD123 or PSMA in hematological malignancies and solid tumors.
Standard CAR-T cells depend on the presence and direct binding of cancer antigens for activation and proliferation.
A key feature of our Universal Switchable CAR assets is a switchable turn-on/-off mechanism. If desired, the off-switch is designed to act very rapidly (T cell silencing in less than 4 hours) determined by the short pharmacokinetic half-life and fast internalization of soluble adaptors called Targeting Modules (TMs).
These TMs provide the antigen specificity to redirect and activate gene-modified T cells, engineered to express a universal CAR against tumor antigens. TMs consist of a highly flexible antigen-binding moiety, linked to a motif recognized by the universal CAR.
Universal Switchable CARs can overcome through switchability the risk of acute and long-term CRS-related side effects, opening an improved therapeutic window for clinical application. Our Universal Switchable CARs were designed to have a reduced susceptibility for immunosuppression by Tregs through utilizing CD28 instead of 4-1BB in the intracellular signaling domain of the CAR. TMs efficiently penetrate and rapidly accumulate within solid tumors, allowing for potent recruitment of Universal Switchable CARs into tumor tissue and an efficient anti-tumor response.
Compared to standard CAR-T cells, the Universal Switchable CAR platform allows for excellent controllability of CAR-T reactivity while maintaining high anti-tumor activity, preventing T cell exhaustion and immune-suppression.
Phase I studies of our first Universal Switchable CAR assets AVC-101 for the treatment of AML and AVC-102 directed against prostate cancer are ongoing and have provided clinical validation for the platform.
