New anti-CD30 human pancreatic ribonuclease-based immunotoxin reveals strong and specific cytotoxicity in vivo.
Although the therapy of Hodgkin lymphoma and anaplastic large cell lymphoma has been considerably improved during the last decades, high therapeutic toxicity, relapses, secondary tumors, and primary treatment failure(s) occur. Both malignancies are well suited for CD30-targeted immunotherapy because of their strong CD30 expression. We constructed an immunotoxin composed of a single chain variable fragment of a CD30 antibody fused to the human pancreatic ribonuclease, showing CD30-specific binding and ribonucleolytic activity resistant to the inhibitor RNasin. This immunotoxin revealed CD30-specific anti-tumor activity in BALB/c mice that were challenged with CD30-positive or CD30-negative syngeneic tumor cells.
Braschoss
Sandra
S
Institut für Pathologie, Charité--Campus Benjamin Franklin (FU Berlin), Germany.
Hirsch
Burkhard
B
Dübel
Stefan
S
Stein
Harald
H
Dürkop
Horst
H
D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D004331:Drosophila melanogaster; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D017730:Ki-1 Antigen / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000473:pathology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000276:immunology*; D014185:Transplantation, Isogeneic / Q000473:pathology; D014407:Tumor Cells, Cultured
D003603:Cytotoxins; D000922:Immunotoxins; D017730:Ki-1 Antigen; D011993:Recombinant Fusion Proteins; D012259:Ribonuclease, Pancreatic