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Blood, 1 July 2004, Vol. 104, No. 1, pp. 170-177. Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2003-12-4438. This Article Full Text (PDF) All Versions of this Article: 2003-12-4438v1 104/1/170    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Igarashi, T. Articles by Childs, R. W Search for Related Content PubMed PubMed Citation Articles by Igarashi, T. Articles by Childs, R. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 5, 2004 Accepted February 16, 2004 Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin -like receptor (KIR) ligand incompatibility against melanoma and renal cell carcinoma cells Takehito Igarashi, Jason Wynberg, Ramaprasad Srinivasan, Brian Becknell, John P McCoy, Yoshiyuki Takahashi, Dante A Suffredini, W M Linehan, Michael A Caligiuri, and Richard W Childs* Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Department of Internal Medicine, Division of Hematology/Oncology, The Ohio State University, Columbus, OH, USA Flow Cytometry Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: childsr{at}nhlbi.nih.gov. Cellular inactivation through killer Ig-like receptors (KIR) may allow neoplastic cells to evade host NK-cell-mediated immunity. Recently, alloreactive NK-cells were shown to mediate anti-leukemic effects against AML after mismatched-transplantation when KIR-ligand incompatibility existed in the direction of GVHD. Therefore, we investigated if solid tumor cells would have similar enhanced susceptibility to allogeneic KIR-incompatible NK-cells compared to their KIR-matched autologous or allogeneic counterparts. NK populations enriched and cloned from the blood of cancer patients or healthy donors homozygous for HLA-C alleles in either group-1 (C-G1) or group-2 (C-G2) were tested in-vitro for cytotoxicity against EBV-LCL, renal cell carcinoma (RCC) and melanoma (MEL) cells possessing or lacking a matching KIR-inhibitory HLA-C ligand. Allogeneic NK-cells were more cytotoxic to tumor targets mismatched for KIR-ligands than their KIR-ligand matched counterparts. Bulk NK populations (CD3-/CD2+/CD56+) expanded 104-fold from patients homozygous for C-G1 or C-G2 had enhanced cytotoxicity against KIR-ligand mismatched tumor cells but only minimal cytotoxicity against KIR-ligand matched targets. Further, NK-cell lines from C-G1 or C-G2 homozygous cancer patients or healthy donors were expanded that failed to kill autologous or KIR-matched MEL and RCC cells yet had significant cytotoxicity (i.e. >50% lysis at 20:1 E:T ratio) against allogeneic KIR-mismatched tumor lines. These data suggest KIR-incompatible allogeneic NK-cells might have superior immunotherapeutic effects against solid tumors compared to investigational approaches which use autologous NK-cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. J. Rose, A. G. Brooks, L. A. Stewart, T. H. Nguyen, and A. P. Schwarer Killer Ig-Like Receptor Ligand Mismatch Directs NK Cell Expansion In Vitro J. 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