Activity of anti-erbB-2 recombinant toxin OLX-209 on lung cancer cell lines in the absence of erbB-2 gene amplification.
The recombinant oncotoxin OLX-209 [e23(Fv)PE38KDEL] has been developed to target cancers with erbB-2 expression and is nearing a clinical trial. Important in clinical planning is the selection of patients on the basis of tumor expression of erbB-2. ErbB-2 gene amplification occurs in cancers of the breast, stomach, and ovary. Patients with these diseases and evident overexpression are candidates for OLX-209 therapy. In lung cancer, overexpression of erbB-2 is also frequent, but in most cases, it is not caused by gene amplification. This study demonstrates that OLX-209 has activity on lung cancer cells with varying levels of erbB-2 expression in the presence and absence of gene amplification. In vitro sensitivity of cell lines to OLX-209 is related to erbB-2 expression level. Normal bronchial epithelial cells were not sensitive. Effective treatment of lung cancer cell lines growing as xenografts in nude mice was shown with Calu-3 (a lung adenocarcinoma line with high levels of p185(erbB-2) caused by gene amplification) and three other lung adenocarcinomas (A549, NCI-H1466, and 201T) with lower levels of p185(erbB-2) and no gene amplification. The 201T cell line was isolated recently from a lung tumor with erbB-2 expression in the original tumor. The results of this study indicate that patients with erbB-2-positive, non-small cell lung cancer should be included in clinical trials of OLX-209.
Kasprzyk
P G
PG
Argonex Pharmaceuticals, Inc., The Woodlands, Texas 77381, USA.
Sullivan
T L
TL
Hunt
J D
JD
Gubish
C T
CT
Scoppa
C A
CA
Oelkuct
M
M
Bird
R
R
Fischer
P H
PH
Siegfried
J M
JM
King
C R
CR
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000906:Antibodies; D005098:Exotoxins; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D057127:Single-Chain Antibodies; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000906:Antibodies; D005098:Exotoxins; D000922:Immunotoxins; C089922:OLX 209; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies