Carbohydrate vaccines that induce antibodies against cancer. 1. Rationale |
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Authors: | Philip O. Livingston Shengle Zhang Kenneth O. Lloyd |
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Affiliation: | (1) Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York City, NY 10021, USA, US |
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Abstract: | Resistance to chemotherapy is a major cause for failure in the treatment of lung cancer. Compared to conventional cytotoxic drugs, immunotoxins act by different mechanisms and thus might be promising for the treatment of chemoresistant cancer. The monoclonal antibody MOC31 recognises the epithelial glycoprotein-2 (EGP-2), a cell-surface antigen associated with small-cell lung cancer (SCLC) and a major fraction of lung adenocarcinomas. An immunotoxin composed of MOC31 and a recombinant form of Pseudomonas exotoxin A lacking the cell-binding domain (ETA252 – 613) was prepared, and its effect on lung cancer cell lines examined. MOC31-ETA252 – 613 was selectively cytotoxic to EGP-2-positive SCLC and adenocarcinoma cell lines inhibiting proliferation by 50% at concentrations ranging from 0.01 nM to 0.3 nM. Moreover, the immunotoxin reduced the numberof clonogenic tumour cells from cultures by factors of 104 and 105 during a 24-h and a 3-week exposure respectively. In athymic mice, the immunotoxin, which revealed a serum half-life of approximately 4 h, caused substantial regression of small (40 mm3) chemoresistant tumour xenografts and significantly delayed the growth of larger tumours (120 mm3). This finding indicates that MOC31-ETA252 – 613 may be useful for the treatment of lung cancer in the setting of chemoresistant minimal residual disease. Received: 31 October 1996 / Accepted: 5 December 1996 |
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Keywords: | Small-cell lung cancer Lung adenocarcinoma Chemoresistance Epithelial glycoprotein-2 Immunotoxin |
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