1. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies.
- Author
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Kohrt, Holbrook E., Thielens, Ariane, Marabelle, Aurelien, Sagiv-Barfi, Idit, Sola, Caroline, Chanuc, Fabien, Fuseri, Nicolas, Bonnafous, Cecile, Czerwinski, Debra, Rajapaksa, Amanda, Waller, Erin, Ugolini, Sophie, Vivier, Eric, Romagne, Francois, Levy, Ronald, Blery, Mathieu, and Andre, Pascale
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KILLER cells , *CD20 antigen , *LYMPHOMA treatment , *CELL-mediated cytotoxicity , *RITUXIMAB , *B cells - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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