FCGR2A Polymorphism Is Correlated With Clinical Outcome After Immunotherapy of Neuroblastoma With Anti-GD2 Antibody and Granulocyte Macrophage Colony-Stimulating Factor

抗体依赖性细胞介导的细胞毒性 医学 免疫学 神经母细胞瘤 免疫疗法 抗体 基因型 队列 粒细胞巨噬细胞集落刺激因子 内科学 单克隆抗体 生物 细胞培养 基因 细胞因子 免疫系统 遗传学
作者
Nai‐Kong V. Cheung,Rebecca Sowers,Andrew J. Vickers,Irene Y. Cheung,Brian H. Kushner,Richard Görlick
出处
期刊:Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:24 (18): 2885-2890 被引量:117
标识
DOI:10.1200/jco.2005.04.6011
摘要

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.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.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).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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