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Genotypes of NK cell KIR Receptors, Their Ligands, and Fc? Receptors in the Response of Neuroblastoma Patients to Hu14.18-IL2 Immunotherapy

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dc.contributor.author Maris, JM
dc.contributor.author Seeger, RC
dc.contributor.author London, WB
dc.contributor.author DeSantes, KB
dc.contributor.author Gadbaw, B
dc.contributor.author Yang, R
dc.contributor.author Reisfeld, RA
dc.contributor.author Gillies, SD
dc.contributor.author Shusterman, S
dc.contributor.author Kim, K
dc.contributor.author Seo, S
dc.contributor.author Gan, J
dc.contributor.author Lorentzen, D
dc.contributor.author Kolesar, J
dc.contributor.author Hank, JA
dc.contributor.author Delgado, DC
dc.contributor.author Sondel, Paul
dc.date.accessioned 2011-08-23T19:58:57Z
dc.date.available 2011-08-23T19:58:57Z
dc.date.issued 2010-12-01
dc.identifier.uri http://digital.library.wisc.edu/1793/54147
dc.description PMID: 20935224 en
dc.description.abstract Response to immunocytokine (IC) therapy is dependent on natural killer cells in murine neuroblastoma (NBL) models. Furthermore, killer immunoglobulin-like receptor (KIR)/KIR-ligand mismatch is associated with improved outcome to autologous stem cell transplant for NBL. Additionally, clinical antitumor response to monoclonal antibodies has been associated with specific polymorphic-Fc?R alleles. Relapsed/refractory NBL patients received the hu14.18-IL2 IC (humanized anti-GD2 monoclonal antibody linked to human IL2) in a Children's Oncology Group phase II trial. In this report, these patients were genotyped for KIR, HLA, and FcR alleles to determine whether KIR receptor-ligand mismatch or specific Fc?R alleles were associated with antitumor response. DNA samples were available for 38 of 39 patients enrolled: 24 were found to have autologous KIR/KIR-ligand mismatch; 14 were matched. Of the 24 mismatched patients, 7 experienced either complete response or improvement of their disease after IC therapy. There was no response or comparable improvement of disease in patients who were matched. Thus KIR/KIR-ligand mismatch was associated with response/improvement to IC (P = 0.03). There was a trend toward patients with the Fc?R2A 131-H/H genotype showing a higher response rate than other Fc?R2A genotypes (P = 0.06). These analyses indicate that response or improvement of relapsed/refractory NBL patients after IC treatment is associated with autologous KIR/KIR-ligand mismatch, consistent with a role for natural killer cells in this clinical response. en
dc.description.provenance Submitted by Julie Schneider (jschneider@library.wisc.edu) on 2011-08-23T19:58:57Z No. of bitstreams: 1 Sondel_Cancer Research_2010.doc: 302080 bytes, checksum: a02435425f2b063c10df9dfd2f970c9d (MD5) en
dc.description.provenance Made available in DSpace on 2011-08-23T19:58:57Z (GMT). No. of bitstreams: 1 Sondel_Cancer Research_2010.doc: 302080 bytes, checksum: a02435425f2b063c10df9dfd2f970c9d (MD5) Previous issue date: 2010-12-01 en
dc.title Genotypes of NK cell KIR Receptors, Their Ligands, and Fc? Receptors in the Response of Neuroblastoma Patients to Hu14.18-IL2 Immunotherapy en
dc.type Article en

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