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 linked to PE38, a genetically engineered form of Pseudomonas exotoxin. B3 recognizes a carbohydrate antigen (Le(Y)) present on many human solid tumors. LMB-1 has excellent antitumor activity in nude mice bearing Le(Y)-positive tumors. We conducted a phase I study of 38 patients with solid tumors who failed conventional therapy and whose tumors expressed the Le(Y) antigen. Objective antitumor activity was observed in 5 patients, 18 had stable disease, 15 progressed. A complete remission was observed in a patient with metastatic breast cancer to supraclavicular nodes. A greater than 75% tumor reduction and resolution of all clinical symptoms lasting for more than six months was observed in a colon cancer patient with extensive retroperitoneal and cervical metastasis. Three patients (two colon, one breast cancer) had minor responses. The maximum tolerated dose of LMB-1 is 75 microgram/kg given intravenously 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 evaluated in clinical studies for more than two decades, this is the first report of antitumor activity in epithelial tumors.
Pai
L H
LH
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Wittes
R
R
Setser
A
A
Willingham
M C
MC
Pastan
I
I
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004361:Drug Tolerance; D005098:Exotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007983:Lewis Blood Group Antigens; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D014057:Tomography, X-Ray Computed; D014652:Vascular Diseases / Q000209:etiology
D000911:Antibodies, Monoclonal; D005098:Exotoxins; D000922:Immunotoxins; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen