FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor.
J Clin Oncol
; 24(18): 2885-90, 2006 Jun 20.
Article
in En
| MEDLINE
| ID: mdl-16682723
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 ANDMETHODS:
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin G
/
Granulocyte-Macrophage Colony-Stimulating Factor
/
Immunization, Passive
/
Receptors, IgG
/
Antibodies, Monoclonal
/
Neuroblastoma
Type of study:
Etiology_studies
/
Guideline
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Child
/
Child, preschool
/
Humans
/
Infant
Language:
En
Journal:
J Clin Oncol
Year:
2006
Document type:
Article
Affiliation country:
United States