About This Item

Ask the MINDS@UW Librarian

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

Show full item record

File(s):

Author(s)
Maris, JM; Seeger, RC; London, WB; DeSantes, KB; Gadbaw, B; Yang, R; Reisfeld, RA; Gillies, SD; Shusterman, S; Kim, K; Seo, S; Gan, J; Lorentzen, D; Kolesar, J; Hank, JA; Delgado, DC; Sondel, Paul
Date
Dec 01, 2010
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.
Description
PMID: 20935224
Permanent link
http://digital.library.wisc.edu/1793/54147 
Export
Export to RefWorks 
‚Äč

Part of

Show full item record

Search and browse




About MINDS@UW

Deposit materials

  1. Register to deposit in MINDS@UW
  2. Need deposit privileges? Contact us.
  3. Already registered? Have deposit privileges? Deposit materials.