Kinetic events involved in immunotoxin-antigen binding and intracellular trafficking.

Each yellow arrow indicates a kinetic step of the model. The tumor cell sheds the surface antigen and the surface complexed antigen at a certain rate. The immunotoxin molecule exiting from the capillary diffuses in the extra-cellular space and binds to either the surface antigen or shed antigen by the association reaction between the antigen and immunotoxin. The surface-bound immunotoxin is internalized by the receptor-mediated endocytosis and mostly inactivated in the endosomal stage. The surviving toxin translocates to the cytosol, where the toxin inhibits protein synthesis and eventually causes cell death. In non-intoxicated cells, the antigen is replenished by fresh protein synthesis.