• Ann. Thorac. Surg. · Nov 1996

    c-erbB-2/p185-directed therapy in human lung adenocarcinoma.

    • J M Snider, L J Bushnell, L C Chen, and L A Lanza.
    • Division of Cardiothoracic Surgery, University of Iowa Hospitals and Clinics, Iowa City, USA.
    • Ann. Thorac. Surg. 1996 Nov 1; 62 (5): 1454-9.

    BackgroundThese experiments were conducted to determine whether p185 can be therapeutically targeted in adenocarcinoma of the lung using an anti-p185-gelonin conjugate. c-erbB-2/p185 is overexpressed in up to one third of non-small cell lung cancers. CALU-3 is a human lung adenocarcinoma cell line that overexpresses p185. muMoAb-4D5 is a murine anti-p185 monoclonal immunoglobulin G1. Gelonin is a potent type 1 ribosomal inhibitory protein.Methods4D5 and gelonin were covalently modified and linked. Purification was confirmed by SDS-polyacrylamide gel electrophoresis. Dose-dependent cytotoxicity was quantified using 3H-thymidine uptake by CALU-3 cells after incubation with 4D5-gelonin conjugate or with control substances (4D5, gelonin, unconjugated 4D5 + gelonin, or control antibody MOPC-21).ResultsThe 4D5-gelonin conjugate showed a 50% inhibitory concentration of 3.5 x 10(-10) mol/L, but 4D5 alone demonstrated no cytotoxic effect. Gelonin and the unconjugated 4D5-gelonin mixture had one tenth the cytotoxicity of the 4D5-gelonin conjugate (inhibitory concentration = 6.5 x 10(-9) mol/L and 8.5 x 10(-9) mol/L, respectively). The conjugate exhibited minimal toxicity against a p185-negative cell line (NIH3T3).ConclusionsSelective and efficient killing of human lung adenocarcinoma cells can be achieved in vitro using c-erbB-2/p185-directed therapy.

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