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

Nai Kong V Cheung, Rebecca Sowers, Andrew J. Vickers, Irene Y. Cheung, Brian H. Kushner, Richard Gorlick

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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.

Original languageEnglish (US)
Pages (from-to)2885-2890
Number of pages6
JournalJournal of Clinical Oncology
Volume24
Issue number18
DOIs
StatePublished - Jun 20 2006

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Granulocyte-Macrophage Colony-Stimulating Factor
Antibody-Dependent Cell Cytotoxicity
Neuroblastoma
Immunotherapy
Anti-Idiotypic Antibodies
Phagocytes
Polymerase Chain Reaction
Reverse Transcription
Bone Marrow
Alleles
Genotype
Disease-Free Survival
Histology
Immunoglobulin G
Recurrence
Antibodies
DNA
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. / Cheung, Nai Kong V; Sowers, Rebecca; Vickers, Andrew J.; Cheung, Irene Y.; Kushner, Brian H.; Gorlick, Richard.

In: Journal of Clinical Oncology, Vol. 24, No. 18, 20.06.2006, p. 2885-2890.

Research output: Contribution to journalArticle

Cheung, Nai Kong V ; Sowers, Rebecca ; Vickers, Andrew J. ; Cheung, Irene Y. ; Kushner, Brian H. ; Gorlick, Richard. / FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 18. pp. 2885-2890.
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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.",
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AU - Kushner, Brian H.

AU - Gorlick, Richard

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N2 - 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.

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