| Literature DB >> 24326534 |
Holbrook E Kohrt1, Ariane Thielens, Aurelien Marabelle, Idit Sagiv-Barfi, Caroline Sola, Fabien Chanuc, Nicolas Fuseri, Cécile Bonnafous, Debra Czerwinski, Amanda Rajapaksa, Erin Waller, Sophie Ugolini, Eric Vivier, François Romagné, Ronald Levy, Mathieu Bléry, Pascale André.
Abstract
Natural killer (NK) cells mediate antilymphoma activity by spontaneous cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when triggered by rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. The balance of inhibitory and activating signals determines the magnitude of the efficacy of NK cells by spontaneous cytotoxicity. Here, using a killer-cell immunoglobulin-like receptor (KIR) transgenic murine model, we show that blockade of the interface of inhibitory KIRs with major histocompatibility complex (MHC) class I antigens on lymphoma cells by anti-KIR antibodies prevents a tolerogenic interaction and augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces enhanced NK-cell-mediated, rituximab-dependent cytotoxicity against lymphoma in vitro and in vivo in KIR transgenic and syngeneic murine lymphoma models. These results support a therapeutic strategy of combination rituximab and KIR blockade through lirilumab, illustrating the potential efficacy of combining a tumor-targeting therapy with an NK-cell agonist, thus stimulating the postrituximab antilymphoma immune response.Entities:
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Year: 2013 PMID： 24326534 PMCID： PMC3907754 DOI： 10.1182/blood-2013-08-519199
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113