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|Title:||Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.|
|Authors:||Scott, Andrew M;Lee, Fook-Thean;Hopkins, Wendie;Cebon, Jonathan S;Wheatley, J M;Liu, Z;Smyth, Fiona E;Murone, Carmel;Sturrock, S;MacGregor, Duncan;Hanai, N;Inoue, K;Yamasaki, M;Brechbiel, Martin W;Davis, Ian D;Murphy, R;Hannah, A;Lim-Joon, M;Chan, T;Chong, Geoffrey;Ritter, G;Hoffman, E W;Burgess, Antony W;Old, Lloyd J|
|Affiliation:||Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, and Department of Nuclear Medicine and Centre for Positron Emission Tomography, Surgery, and Anatomical Pathology, Melbourne, Australia|
|Citation:||Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology; 19(19): 3976-87|
|Abstract:||KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma.Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10.Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period.This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.|
|Internal ID Number:||11579119|
Antibodies, Monoclonal.adverse effects.immunology.pharmacokinetics.therapeutic use
Indium Radioisotopes.diagnostic use
Recombinant Fusion Proteins.adverse effects.immunology.pharmacokinetics.therapeutic use
|Appears in Collections:||Journal articles|
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