Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy

David C. Delgado, Jacquelyn A. Hank, Jill Kolesar, David Lorentzen, Jacek Gan, Songwon Seo, Kyung Mann Kim, Suzanne Shusterman, Stephen D. Gillies, Ralph A. Reisfeld, Richard Yang, Brian Gadbaw, Kenneth B. DeSantes, Wendy B. London, Robert C. Seeger, John M. Maris, Paul M. Sondel

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

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-FcγR 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 FcγR 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 FcγR2A 131-H/H genotype showing a higher response rate than other FcγR2A 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.

Original languageEnglish
Pages (from-to)9554-9561
Number of pages8
JournalCancer Research
Volume70
Issue number23
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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