Masked ImmunoCytokines (MICs)
MICs: Next Generation ImmunoCytokines
Masked Immunocytokines (MICs) are tumor antigen-targeting antibodies fused to a cytokine which delivers direct anti-tumor killing capability as well as immune response-initiating activity. The cytokine is masked to inhibit systemic activation, and the mask is designed to selectively cleave within the tumor microenvironment. This design facilitates more robust delivery of the cytokine to the tumor, while inhibiting systemic effects. MICs can be designed with different antibodies to target a variety of tumor antigens, and with a variety of different cytokines.
Design of a MIC
MICs are compromised of a masked cytokine fused to an antibody that targets a tumor antigen.
Cytokines are essential mediators of anti-cancer immunity. In addition to their direct anti-proliferative effects against many cancers, cytokines can have a multitude of immunotherapeutic effects including enhancement of CD8+ T cell and natural killer (NK) cell cytotoxicity, dendritic cell maturation, and suppression of regulatory T cells.
Targeting the tumor antigen enhances retention within the tumor, and localizes the fused cytokine to the tumor cell surface.
A peptide mask is attached to the C-terminal end of the cytokine via a tumor-selective protease cleavable linker. This structure allows the mask to compete with the cytokine's receptor until the antibody binds to the antigen on the tumor cell surface, allowing tumor proteases to cut off the mask and activate the cytokine.