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Immunology

Abstract 5586: NK cell killer Ig-like receptor (KIR) genotype as a novel biomarker for neuroblastoma patients receiving Anti-GD2 monoclonal antibody 3F8

Jeffrey M. Venstrom, Junting Zheng, Brian H. Kushner, Shakeel Modak, Karen E. Danis, Irene Y. Cheung, Bo Dupont, Nai-Kong Cheung and Katharine C. Hsu
Jeffrey M. Venstrom
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Junting Zheng
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Brian H. Kushner
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Shakeel Modak
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Karen E. Danis
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Irene Y. Cheung
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Bo Dupont
2Sloan-Kettering Institute for Cancer Research, New York, NY.
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Nai-Kong Cheung
1Memorial Sloan-Kettering Cancer Center, New York, NY
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Katharine C. Hsu
1Memorial Sloan-Kettering Cancer Center, New York, NY
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DOI: 10.1158/1538-7445.AM10-5586 Published April 2010
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Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

Abstract

Background: Natural killer (NK) cells are regulated by inhibitory killer Ig-like receptors (KIRs) that recognize specific HLA class I ligands. KIR-HLA genotypes are tightly linked to NK cell function and clinical outcomes in allogeneic and autologous hematopoietic stem cell transplantation (HSCT). Because NK cells contribute to antibody-dependent cellular cytotoxicity, we hypothesized that specific KIR-HLA genotypes may predict NK cell responsiveness to mAb therapy, and thus, may be useful clinically to identify patients likely to respond to mAb therapy. Methods: 76 children with high risk neuroblastoma received cyclophosphamide-containing induction chemotherapy followed by murine IgG3 monoclonal antibody 3F8 against ganglioside GD2 between 1993 and 2007. HLA and KIR genotyping was performed, and patients were segregated into KIR-HLA groups based on known functional KIR-HLA ligand relationships: KIR2DL2/2DL3 with HLA-CAsn80(HLA-C1 group), KIR2DL1 with HLA-C Lys80(HLA-C2 group), and KIR3DL1 with HLA-Bw4. Overall survival and progression-free survival were estimated by Kaplan-Meier method and hazard ratios by Cox regression. No adjustments were made for multiple comparisons. Comparisons of each end point were based on the log-rank statistics. Results: 63% of the 76 children lacked at least 1 HLA ligand for his/her inhibitory KIR. At 3 years, 80% of patients lacking any KIR ligand (n=46) were alive compared with 69% of patients with all HLA ligands present (n=30) (HR 0.41; 95% CI 0.17-0.98; P=0.04). 23/23 (100%) patients specifically lacking the HLA-Bw4 ligand for KIR3DL1 were alive at 3 years compared with 34/52 (67%) patients exhibiting HLA-Bw4 for KIR 3DL1 (n=52) (HR 0.20; 95% CI 0.05-0.87; P=0.02). Conclusion: KIR-HLA immunogenetics may be a novel biomarker for neuroblastoma patients receiving chemo-immunotherapy. The milieu of HSCT may not be required for NK cells to behave according to “missing ligand,” and KIR-HLA combinations may be predictive of outcome for other malignancies similarly treated with mAb.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5586.

  • ©2010 American Association for Cancer Research
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Cancer Research: 70 (8 Supplement)
April 2010
Volume 70, Issue 8 Supplement
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Abstract 5586: NK cell killer Ig-like receptor (KIR) genotype as a novel biomarker for neuroblastoma patients receiving Anti-GD2 monoclonal antibody 3F8
Jeffrey M. Venstrom, Junting Zheng, Brian H. Kushner, Shakeel Modak, Karen E. Danis, Irene Y. Cheung, Bo Dupont, Nai-Kong Cheung and Katharine C. Hsu
Cancer Res April 15 2010 (70) (8 Supplement) 5586; DOI: 10.1158/1538-7445.AM10-5586

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Abstract 5586: NK cell killer Ig-like receptor (KIR) genotype as a novel biomarker for neuroblastoma patients receiving Anti-GD2 monoclonal antibody 3F8
Jeffrey M. Venstrom, Junting Zheng, Brian H. Kushner, Shakeel Modak, Karen E. Danis, Irene Y. Cheung, Bo Dupont, Nai-Kong Cheung and Katharine C. Hsu
Cancer Res April 15 2010 (70) (8 Supplement) 5586; DOI: 10.1158/1538-7445.AM10-5586
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