Treatment of advanced solid tumors with immunotoxin LMB–1: An antibody linked to Pseudomonas exotoxin (original) (raw)

Nature Medicine volume 2, pages 350–353 (1996)Cite this article

Abstract

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 (LeY) present on many human solid tumors1. LMB–1 has excellent antitumor activity in nude mice bearing LeY–positive tumors2. We conducted a phase I study of 38 patients with solid tumors who failed conventional therapy and whose tumors expressed the LeY 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 μg/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.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA
    Lee H. Pai & Ira Pastan
  2. Medicine Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA
    Robert Wittes & Ann Setser
  3. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, 29425, USA
    Mark C. Willingham

Authors

  1. Lee H. Pai
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  2. Robert Wittes
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  3. Ann Setser
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  4. Mark C. Willingham
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  5. Ira Pastan
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Pai, L., Wittes, R., Setser, A. et al. Treatment of advanced solid tumors with immunotoxin LMB–1: An antibody linked to Pseudomonas exotoxin.Nat Med 2, 350–353 (1996). https://doi.org/10.1038/nm0396-350

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