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Ann Thorac Surg 1996;62:1454-1459
© 1996 The Society of Thoracic Surgeons

Original Article: General Thoracic

c-erbB-2/p185–Directed Therapy in Human Lung Adenocarcinoma

John M. Snider, MD, Lamar J. Bushnell, MD, Lih C. Chen, BA, Louis A. Lanza, MD

Division of Cardiothoracic Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Background. These 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.

Methods. 4D5 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).

Results. The 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).

Conclusions. Selective and efficient killing of human lung adenocarcinoma cells can be achieved in vitro using c-erbB-2/p185–directed therapy.


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Discussion
Ann. Thorac. Surg. 1996 62: 1459. [Extract] [Full Text]





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