TREATMENT OF ADVANCED SOLID TUMORS WITH IMMUNOTOXIN LMB-1 - AN ANTIBODY LINKED TO PSEUDOMONAS EXOTOXIN

Immunotoxin LMB-1 is composed of monoclonal antibody B3 chemically lin ked to PE38, a genetically engineered form of Pseudomonas exotoxin. B3 recognizes a carbohydrate antigen (Le(Y)) present on many human solid tumors(1). LMB-1 has excellent antitumor activity in nude mice bearin g Le(Y)-positive tumors(2). We conducted a phase I study of 38 patient s with solid tumors who failed conventional therapy and whose tumors e xpressed the Le(Y) antigen. Objective antitumor activity was observed in 5 patients, 18 had stable disease, 15 progressed. A complete remiss ion was observed in a patient with metastatic breast cancer to supracl avicular nodes. A greater than 75% tumor reduction and resolution of a ll clinical symptoms lasting for more than six months was observed in a colon cancer patient with extensive retroperitoneal and cervical met astasis. Three patients (two colon, one breast cancer) had minor respo nses. The maximum tolerated dose of LMB-1 is 75 mu g/kg given intraven ously three times every other day. The major toxicity is vascular leak syndrome manifested by hypoalbuminemia, fluid retention, hypotension and, in one case, pulmonary edema. Although immunotoxins have been eva luated in clinical studies for more than two decades, this is the firs t report of antitumor activity in epithelial tumors.