Abstract 1207: Pharmacodynamic evaluation of ADCC mediated effects in humanized IL2 or IL15 NOG mice models

Abstract

Abstract Humanized mice (i.e. immunodeficient NOG mice engrafted with human hematopoietic stem cells (HSC)) have demonstrated their usefulness for studying the human immune system. These models should help recapitulating some pathology such as viral infection and then are suitable system to evaluate new human specific therapies. Nevertheless, one issue of these models is the incomplete maturation of natural killer (NK) cell subpopulation. This lake of NK cell functionality was solved by the Central Institute for Experimental Animals (CIEA) with the second generation of transgenic NOG mice expressing human IL2 or IL15 (NK-NOG). The serum levels of hIL-2 and hIL-15 in mice were 1-2 and 0.1-0.2 ng/mL, respectively. In these mice, human NK cells differentiated from HSC are well distributed in the mouse body (peripheral blood, bone marrow, spleen…). They expressed various NK receptors such as NKp30, NKp44, NKp46, etc., granzyme A and perforin, indicating their maturity in the mice. They are also fully functional as evidenced using an ex vivo 51Cr release assay demonstrating lysis properties of human NK cells from collected spleen of HSC-humanized mice.In vivo proof of concept studies were successfully performed with humanized NK-NOG mice xenografted with either human Burkitt's disseminated lymphoma cells or with human solid tumors treated with humanized therapeutic antibodies. Prediction of ADCC-mediated antitumor activity of humanized antibodies is now routinely feasible for preclinical evaluation using these new in vivo NK-NOG models. Citation Format: Caroline Mignard, Jean-Francois Mirjolet, Olivier Duchamp, Yasuyuki Ohnishi, Ikumi Katano, Mamoru Ito. Pharmacodynamic evaluation of ADCC mediated effects in humanized IL2 or IL15 NOG mice models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1207. doi:10.1158/1538-7445.AM2014-1207