Aggressive administration of recombinant oncotoxin AR209 (anti-ErbB-2) in athymic nude mice implanted with orthotopic human non-small cell lung tumours.
Lung cancer remains a significant public health problem in the U.S.A. and will result in an estimated 160,400 deaths in 1997. This appalling number is due in large part to the lack of adequate treatment for tumours that are refractory to surgery with curable intent, or of an adequate salvage therapy for those patients who recur after surgical resection. Because non-small cell lung cancer is refractory to traditional chemotherapy, non-traditional therapies have been developed to treat patients with this disease. Recombinant oncotoxins have been designed to target cells that express certain proteins as part of their cellular membrane. One such oncotoxin, AR209 (formerly OLX-209 [e23(Fv)PE38KDEL]), has the specificity of an anti-ErbB-2 antibody contained within a single-chain antibody domain (e23v) coupled to a portion of the Pseudomonas exotoxin A (PE38KDEL). Previous studies demonstrate that this drug is capable of significantly reducing the size of orthotopic lung tumour xenografts. However, most of the treated mice developed tumours once therapy was removed. In this study, mice were treated aggressively using one of four drug treatment schedules. Mice were treated with either intravenous or subcutaneous injections of AR209 over a 2 week period. The data indicate that AR209 significantly reduced the size of tumours and upon microscopic analysis at necropsy, some mice were cured. However, despite the treatment schedule used, many mice contained residual tumour. Residual tumours expressed the ErbB-2 protein, indicating that more aggressive treatment with AR209 may have resulted in higher rates of cure.
Skrepnik
N
N
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112, USA.
Zieske
A W
AW
Robert
E
E
Bravo
J C
JC
Mera
R
R
Hunt
J D
JD
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D018734:Genes, erbB-2 / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual; D011994:Recombinant Proteins / Q000627:therapeutic use*
D000906:Antibodies; D011994:Recombinant Proteins