@phdthesis{Jensen2019,
  author    = {Jensen, Christian},
  title     = {Impact of FCGR Polymorphisms and KIR/HLA Mismatch on outcome following Immunotherapy of Neuroblastoma patients with ch14.18/CHO combination with IL-2},
  institution = {Klinik und Poliklinik f{\"u}r Kinder- und Jugendmedizin},
  school    = {Universit{\"a}t Greifswald, Universit{\"a}tsmedizin},
  pages     = {135},
  year      = {2019},
  abstract  = {Neuroblastoma (NB) is an aggressive, poorly immunogenic tumor in childhood. Therapy for high-risk NB remains challenging. Immunotherapy with anti-GD 2 antibody ch14.18/CHO effectively prolongs the survival of NB patients. Killer-immunoglobulin-like receptor (KIR)/human leucocyte antigen (HLA) mismatch and Fc gamma receptor (FCGR) polymorphisms are reported to affect antibody-dependent cellular cytotoxicity (ADCC) induced by monoclonal antibodies. To determine whether FCGR polymorphisms and KIR/HLA mismatch are associated with the survival following ch14.18-based immunotherapy, genotyping methods that allow for genotype determination of FCGR2A, -3A, -3B, KIR2DL1, 2DL2, 2DL3, and 3DL1 have been established and applied to the analysis of 53 NB patients treated with ch14.18/CHO. High-affinity polymorphisms of FCGR2A (H131) and FCGR3A (V158) were associated with improved survival. Importantly, patients displaying both the FCGR3A-V158 and FCGR2A-H131 alleles exhibited significantly improved event-free survival. No association was found between KIR/HLA genotypes or FCGR3B alleles and patients' survival in our patient cohort. In conclusion, impact of FCGR2A and -3A genotypes in response to ch14.18/CHO immunotherapy in combination with IL2 was demonstrated. FCGR2A and -3A might therefore provide a prognostic marker when conducting ch14.18/CHO-based immunotherapy.},
  subject      = {Neuroblastom},
  language  = {en}
}