PROTEASE-CLEAVAGE RESISTANT, SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES AND CELL-TARGETED MOLECULES COMPRISING THE SAME

摘要

The present invention provides protease-cleavage resistant molecules comprising Shiga toxin effector polypeptides capable of exhibiting potent, Shiga toxin functions (e.g. subcellular routing and cytotoxicity). The present invention also provides protease-cleavage resistant, cell-targeted molecules for targeting specific cell types, e.g., infected or malignant cells. Certain molecules of the present invention are cytotoxic, and certain cell-targeted molecules of the present invention may be used for the targeted killing of specific cell types and the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeted molecules of the invention exhibit improved,tolerability as compared to related cell-targeted molecules comprising protease-cleavage sensitive, wild-type, Shiga toxin effector polypeptides. The cell-targeted molecules of the invention can deliver additional materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, into the interiors of target cells.