Journal article
Genotypes of NK Cell KIR Receptors, Their Ligands, and Fc gamma Receptors in the Response of Neuroblastoma Patients to Hu14.18-IL2 Immunotherapy
Cancer research (Chicago, Ill.), Vol.70(23), pp.9554-9561
12/01/2010
DOI: 10.1158/0008-5472.CAN-10-2211
PMCID: PMC2999644
PMID: 20935224
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 gamma 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 gamma 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 gamma R2A 131-H/H genotype showing a higher response rate than other Fc gamma 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. Cancer Res; 70(23); 9554-61. (C) 2010 AACR.
Details
- Title: Subtitle
- Genotypes of NK Cell KIR Receptors, Their Ligands, and Fc gamma Receptors in the Response of Neuroblastoma Patients to Hu14.18-IL2 Immunotherapy
- Creators
- David C. Delgado - Children's Oncology GroupJacquelyn A. Hank - Children's Oncology GroupJill Kolesar - Dana-Farber Cancer InstituteDavid Lorentzen - Children's Oncology GroupJacek Gan - Children's Oncology GroupSongwon Seo - Dana-Farber Cancer InstituteKyungMann Kim - Children's Oncology GroupSuzanne Shusterman - Children's Oncology GroupStephen D. Gillies - Children's Oncology GroupRalph A. Reisfeld - Children's Oncology GroupRichard Yang - Scripps Research InstituteBrian Gadbaw - Children's Oncology GroupKenneth B. DeSantes - Children's Oncology GroupWendy B. London - Children's Oncology GroupRobert C. Seeger - Children's Oncology GroupJohn M. Maris - University of PennsylvaniaPaul M. Sondel - Children's Oncology Group
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.70(23), pp.9554-9561
- DOI
- 10.1158/0008-5472.CAN-10-2211
- PMID
- 20935224
- PMCID
- PMC2999644
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 8
- Grant note
- R01-CA-32685-25; P30-CA14520; CA87025; CA81403; RR03186; K12 CA087718 / COG Statistics and Data Center R01CA087025 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Abbie's Fund UL1RR025011 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U10 CA98413 Midwest Athletes for Childhood Cancer Fund Crawdaddy Foundation St. Baldrick's Foundation Evan Dunbar Foundation T32GM008692 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695803002771
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