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Pharmacokinetics of human-mouse chimeric anti-GD2 mAb ch14.18 in a phase I trial in neuroblastoma patients

  • Original Article
  • Chimeric Antibody, Elimination, Kinetics, Half-life, Childhood Tumor
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Abstract

A comprehensive analysis of the pharmacokinetics of human-mouse chimeric anti-ganglioside GD2 antibody mAb ch 14.18 was performed during a phase I clinical trial of ten children with neuroblastoma and one adult with osteosarcoma. The patients received a total of 20 courses of ch 14.18 at dose levels from 10 mg/m2 to 200 mg/m2. The plasma clearance of ch 14.18 was biphasic. Following the first course of treatmentt1/2,α was 3.4±3.1 h andt1/2,β 66.6±27.4 h in 9/10 children. Thet1/2,β values were significantly less than those of 181±73 h previously reported in adult melanoma patients (P<-0.001), and 147.5 h in the adult osteosarcoma patient in our trial. The latter suggests different pharmacokinetics of mAb ch 14.18 in children and adults. After a second course of treatment, administered to 5/10 children,t1/2,β decreased significantly from 72.9±19.8 h to 31.7±18.4 h (P=0.015). We there-fore conclude that the elimination kinetics of mAbs ch 14.18 in children and adults are different, and furthermore that repeated administration of mAb ch 14.18 to children with neuroblastoma leads to accelerated antibody clearance.

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Authors and Affiliations

  1. Charité Kinderklinik, Schumannstr. 20-21, D-10098, Berlin, Germany

    M. M. Uttenreuther-Fischer

  2. Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of California San Diego, 200 West Arbor Drive, USA, 92103-8447, San Diego, California, USA

    M. M. Uttenreuther-Fischer, C. S. Huang & A. L. Yu

  3. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China

    C. S. Huang

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  1. M. M. Uttenreuther-Fischer
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  2. C. S. Huang
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  3. A. L. Yu
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Additional information

This work was supported by grants from FDA, FD-R-000377 and NIH U10 CA 28439, and in part by a grant from the General Clinical Research Center Program, MOI RR00827, of the National Center for Research Resources, National Institutes of Health. M.M.U.-F. and C.S.H. were in part supported by a grant from the Children's Cancer Research Foundation, and M.M.U.-F. was in part supported by a grant of the Kommission für Forschung und wissenschaftlichen Nachwuchs, Charité 95-010/9610766

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Uttenreuther-Fischer, M.M., Huang, C.S. & Yu, A.L. Pharmacokinetics of human-mouse chimeric anti-GD2 mAb ch14.18 in a phase I trial in neuroblastoma patients. Cancer Immunol Immunother 41, 331–338 (1995). https://doi.org/10.1007/BF01526552

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  • DOI: https://doi.org/10.1007/BF01526552

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