FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor Journal Article


Authors: Cheung, N. K. V.; Sowers, R.; Vickers, A. J.; Cheung, I. Y.; Kushner, B. H.; Gorlick, R.
Article Title: FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor
Abstract: Purpose: Anti-GD2 murine IgG3 antibody 3F8 kills neuroblastoma cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte macrophage colony-stimulating factor (GM-CSF) enhances phagocyte-mediated ADCC. The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy. Patients and Methods: The entire cohort of high risk neuroblastoma patients (N = 136) treated on protocol using 3F8 and GM-CSF were the subjects of this analysis. Tumor response was measured by standard clinical tools plus sensitive molecular monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Polymorphic alleles of FCGR2A and FCGR3A were determined by PCR plus direct sequencing using genomic DNA samples obtained from marrow or blood of patients. Results: FCGR2A (R/R) genotype correlated with progression-free survival for the entire cohort (P = .049) and for the subset of patients with no history of prior relapse (P = .023). FCGR2A (R/R) also correlated with marrow remission 2.5 months after treatment initiation: by histology (P = .021 and P = .036, for the entire cohort and the subset, respectively) and by qRT-PCR (P = .052 and P = .033, respectively). Conclusion: The favorable outcome associated with FCGR2A (R/R) genotype is consistent with the proposed role of FCGR2A and phagocyte-mediated ADCC in 3F8 plus GM-CSF immunotherapy. © 2006 by American Society of Clinical Oncology.
Keywords: survival; cancer survival; child; controlled study; human tissue; preschool child; child, preschool; survival analysis; unclassified drug; major clinical study; genetics; histopathology; cancer growth; cancer risk; cancer patient; outcome assessment; cell death; bone marrow cells; reverse transcription polymerase chain reaction; cohort studies; granulocyte macrophage colony stimulating factor; cohort analysis; genotype; cytotoxicity; monoclonal antibody; antibodies, monoclonal; correlation analysis; immunotherapy; immunoglobulin g; infant; neuroblastoma; ganglioside gd2; reverse transcriptase polymerase chain reaction; granulocyte colony stimulating factor receptor; fc receptor; receptors, igg; dna sequence; bone marrow cell; polymorphism, genetic; immunoglobulin g antibody; genetic polymorphism; dna polymorphism; 3f8 antibody; granulocyte-macrophage colony-stimulating factor; passive immunization; immunization, passive; fc gamma receptor 2a; fcgr2a protein, human
Journal Title: Journal of Clinical Oncology
Volume: 24
Issue: 18
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2006-06-20
Start Page: 2885
End Page: 2890
Language: English
DOI: 10.1200/jco.2005.04.6011
PUBMED: 16682723
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 26" - "Export Date: 4 June 2012" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Brian Kushner
    192 Kushner
  2. Nai-Kong Cheung
    447 Cheung
  3. Andrew J Vickers
    565 Vickers
  4. Irene Y Cheung
    75 Cheung
  5. Rebecca S Sowers
    32 Sowers