Immunotoxins are composed of:
Immunotoxins chimeric proteins integrating targeting domain derived monoclonal antibody and cytotoxic domain protein toxin to achieve picomolar potency against malignant cells expressing defined surface antigen. Antibody moiety typically Fab prime 50 kDa scFv 25 kDa composed heavy variable light variable domains connected glycine serine linker disulfide-stabilized Fv dsFv recognizing tumor antigens CD22 135 kDa hairy cell leukemia CD25 IL-2 receptor alpha cutaneous T-cell lymphoma mesothelin 40 kDa GPI-anchored mesothelioma pancreatic adenocarcinoma HER2 with affinity 1-10 nM. Toxin component truncated Pseudomonas exotoxin PE38 38 kDa lacking domain Ia binding LRP1 ubiquitous retaining domain II translocation domain III ADP-ribosylating diphtheria toxin DT388 receptor-binding domain deleted but translocation catalytic retained ricin A chain N-glycosidase depurinating 28S RNA ribosome-inactivating protein saporin Saponaria. Components genetically fused peptide linker GGS chemically conjugated thioether preserving binding enzymatic functions. Upon antigen-mediated endocytosis clathrin-coated pits binding trafficking early endosomes pH 6.0 furin cleavage trans-Golgi network generating heterodimer retrograde via KDEL receptor ER translocation Sec61 cytosol where one molecule sufficient killing cell protein synthesis inhibition triggering apoptosis.
Ref: Pastan Annu Rev Med 2007 Immunotoxin Construction Principles Review; FDA Lumoxiti Moxetumomab Design Label; Janeway Immunotoxin Antibody Toxin Fusion Mechanism.