Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
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
Autore:
Scott, AM; Lee, FT; Hopkins, W; Cebon, JS; Wheatley, JM; Liu, ZQ; Smyth, FE; Murone, C; Sturrock, S; MacGregor, D; Hanai, N; Inoue, K; Yamasaki, M; Brechbiel, MW; Davis, ID; Murphy, R; Hannah, A; Lim-Joon, M; Chan, T; Chong, G; Ritter, G; Hoffman, EW; Burgess, AW; Old, LJ;
Indirizzi:
Austin & Repatriat Med Ctr, Ludwig Inst Canc Res, Melbourne Tumor Biol Branch, Melbourne, Vic, Australia Austin & Repatriat Med Ctr Melbourne Vic Australia ourne, Vic, Australia Austin & Repatriat Med Ctr, Dept Nucl Med, Melbourne, Vic, Australia Austin & Repatriat Med Ctr Melbourne Vic Australia ourne, Vic, Australia Austin & Repatriat Med Ctr, Ctr Positron Emiss Tomog, Melbourne, Vic, Australia Austin & Repatriat Med Ctr Melbourne Vic Australia ourne, Vic, Australia Austin & Repatriat Med Ctr, Dept Surg, Melbourne, Vic, Australia Austin & Repatriat Med Ctr Melbourne Vic Australia ourne, Vic, Australia Austin & Repatriat Med Ctr, Dept Anat Pathol, Melbourne, Vic, Australia Austin & Repatriat Med Ctr Melbourne Vic Australia ourne, Vic, Australia Kyowa Hakko Kogyo Co Ltd, Tokyo, Japan Kyowa Hakko Kogyo Co Ltd Tokyo Japan a Hakko Kogyo Co Ltd, Tokyo, Japan NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA Ludwig Inst Canc Res, New York, NY USA Ludwig Inst Canc Res New York NY USA wig Inst Canc Res, New York, NY USA
Titolo Testata:
JOURNAL OF CLINICAL ONCOLOGY
fascicolo: 19, volume: 19, anno: 2001,
pagine: 3976 - 3987
SICI:
0732-183X(20011001)19:19<3976:STBALO>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
MALIGNANT-MELANOMA; ANTIGENIC SYSTEMS; GD3 GANGLIOSIDE; SURFACE; CELLS; R24; CISPLATIN; BINDING; BREAST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Scott, AM Austin & Repatriat Med Ctr, Ludwig Inst Canc Res, Tumour Targeting Program, Level 1,Harold Stokes Bldg,Studley Rd, Heidelberg, Vic 3084, Australia Austin & Repatriat Med Ctr Level 1,Harold Stokes Bldg,Studley Rd Heidelberg Vic Australia 3084
Citazione:
A.M. Scott et al., "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", J CL ONCOL, 19(19), 2001, pp. 3976-3987

Abstract

Purpose: 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. Patients and Methods: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m(2)). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (In-111) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. Results: 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-, and40-mg/m(2) dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of In-111-KM871 was observed, and tumor uptake of In-111-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy (111)KM871 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 In-111-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. Conclusion: This study is the first to demonstrate the biodistribution andspecific 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. (C) 2001 by American Society of Clinical Oncology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:33:30