Protease cleavage resistance, Shiga toxin A subunit effector polypeptide and cell targeting molecule containing the same

摘要

The present invention provides a protease cleavage resistant molecule comprising a Shiga toxin effector polypeptide capable of exhibiting strong Shiga toxin functions (eg, intracellular routing and cytotoxicity). The present invention also provides protease cleavage resistant, cell targeting molecules that target specific cell types such as infected or malignant cells. Certain molecules of the present invention are cytotoxic, and certain cell targeting molecules of the present invention include a variety of targets including targeted killing of specific cell types, as well as cancer, tumors, developmental abnormalities, immune disorders and microbial infections. Can be used to treat various diseases, disorders and conditions. Certain cell targeting molecules of the present invention exhibit improved in vivo tolerability compared to related cell targeting molecules including protease cleavage sensitive, wild type, Shiga toxin effector polypeptides. The cell targeting molecules of the present invention can deliver additional substances, such as antigens, cytotoxic agents and detection enhancers, into the target cells.