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 made of a cytokine fused with the C-terminus of a tumor antigen-targeting antibody heavy chains.
Tumor antigen targeting enhances tumor retention and localizes the fused cytokine to the target cell surface.
A peptide mask is attached to the C-terminal end of the cytokine, binding it to the antibody and competing with its interaction with its receptor. The mask is attached with a linker that is cleavable by proteases enriched in the tumor microenvironment.
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.