Targeted therapy of schwannoma cells in immunocompetent rats with an erbB2-specific antibody-toxin.
Over-expression of the erbB2-receptor tyrosine kinase is frequently observed in many human tumors of epithelial origin. Due to its causal involvement in malignant transformation and its presence on the tumor cell surface erbB2 is an attractive target for directed tumor therapy. We earlier described the potent anti-tumoral activity of the recombinant single-chain antibody toxin scFv(FRP5)-ETA in vitro and in nude mouse tumor models in vivo. This molecule consists of the variable domains of the heavy and light chains of an erbB2-specific antibody genetically fused to a truncated Pseudomonas exotoxin A. Here we have investigated the in vivo effects of this immunotoxin on erbB2 expressing NV2Cd schwannoma cells growing as s.c. tumors in syngeneic BDIX rats. Established tumors were treated either locally by intra-tumoral injection of scFv(FRP5)-ETA or systemically by injection into the tail vein. Both routes of application resulted in pronounced inhibition of tumor growth with local treatment being more effective. Treatment with 25 micrograms/day of scFv(FRP5)-ETA for 10 days suppressed tumor growth almost completely. Antibodies directed mainly against the toxin domain of the fusion protein developed in all animals treated.
Altenschmidt
U
U
Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, Germany.
Schmidt
M
M
Groner
B
B
Wels
W
W
D036002:ADP Ribose Transferases; D000818:Animals; D000912:Antibodies, Neoplasm / Q000032:analysis; D000918:Antibody Specificity; D001427:Bacterial Toxins; D005098:Exotoxins / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D009442:Neurilemmoma / Q000473:pathology / Q000628:therapy*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000912:Antibodies, Neoplasm; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A