Cytotoxicity of Activated Natural Killer Cells Against Pediatric Solid Tumors.
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Cytotoxicity of Activated Natural Killer Cells Against Pediatric Solid Tumors.

Clin Cancer Res. 2010 Jun 11;

Authors: Cho D, Shook DR, Shimasaki N, Chang YH, Fujisaki H, Campana D

Purpose. To develop new therapies for children with solid tumors, we tested the cytotoxicity of natural killer (NK) cells expanded by coculture with K562-mb15-41BBL cells. We sought to identify the most sensitive tumor subtypes, clarify the molecular interactions regulating cytotoxicity, and determine NK anti-tumor potential in vivo. Experimental Design. We tested in vitro cytotoxicity of expanded NK cells against cell lines representative of Ewing sarcoma (EWS) (n=5), rhabdomyosarcoma (n=4), neuroblastoma (n=3) and osteosarcoma (n=3), and correlated the results with expression of inhibitory and activating NK receptor ligands. We also compared expanded and primary NK cells, determined the effects of activating-receptor ligation and of chemotherapeutic drugs, and assessed the therapeutic effect of NK cell infusions in xenografts.Results. In 45 experiments, EWS and rhabdomyosarcoma cell lines were remarkably sensitive to expanded NK cells, with median cytotoxicities at 1:1 effector:target ratio of 87.2% and 79.1%, respectively. Cytotoxicity was not related to levels of expression of NK receptor ligands, nor was it affected by pretreatment of target cells with daunorubicin or vincristine, but was markedly inhibited by preincubation of NK cells with a combination of antibodies against the NK activating receptors NKGD2 and DNAM-1. Expanded NK cells were considerably more cytototoxic than unstimulated NK cells, and eradicated EWS cells engrafted in NOD/scid IL2RGnull mice.Conclusions. Among pediatric solid tumors, EWS and rhabdomyosarcoma are exquisitely sensitive to expanded NK cells. The NK expansion method described here has been adapted to large-scale conditions, and supports a Phase I clinical study including patients with these malignancies.

PMID: 20542985 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20542985&dopt=Abstract

Posted 16 Jun 2010 4:25 AM by pubmed: neuroblastoma
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