abstract |
The present invention provides amino acid substitutions that confer 1) deimmunization; 2) reduced protease cleavage sensitivity; and / or 3) a heterologous epitope cargo while retaining the functions of Shiga toxin, such as strong cytotoxicity. A polypeptide derived from Shiga toxin A subunit and a cell targeting molecule. Certain polypeptides of the present invention exhibit reduced immunogenicity in mammals and / or can deliver epitopes to MHC class molecules of cells in which the polypeptide is present. Certain molecules comprising the polypeptides of the invention are well tolerated by mammals while retaining one or more of the properties described above. The Shiga toxin polypeptide of the present invention can be used to selectively kill specific cells; as a component of a cell targeting molecule for selectively delivering cargo to specific cells, as well as cancer, immune disorders And as therapeutic and / or diagnostic molecules for treating and diagnosing various conditions, including microbial infections. |