Abstract 1567: Use of humanized NOG mice within the pre-clinical development of new human specific therapies.

Abstract

Abstract Immune cells within the tumor microenvironment are now well recognized as to be targets of interest for cancer treatment. However there are no available pre-clinical models that will accurately support the pre-clinical development of such therapeutic approaches. Humanized NOG (NOD/shi-scid/IL-2Rγnull) mice, bearing human immune cells with or without human target tumor cells, are relevant models to test various therapeutic strategies (e.g. antibody dependent cell cytotoxicity, Treg targeting antibodies, TLR agonists, vaccines, adoptive T cells transfer, …) in various pathologies (e.g. oncology, autoimmune disease, inflammation, transplantation, …). Humanization of NOG mice was already characterized and validated using freshly collected human PBMCs or hematopoietic stem cells (HSCs) in both newborn and adult NOG mice. The complete characterization of the reconstituted NOG mice was done in peripheral blood as well as central lymphoid organs such as bone marrow, spleen and thymus, using FACS analysis. Moreover, the human immune reconstitution and function in NOG mice was also evidenced with human cytokine and immunoglobulin quantification in mouse plasma samples. The injection of mature human PBMC in adult NOG mice leads to the consistent development of a xenogeneic graft-versus-host disease (GvHD), which mimics human GvHD (modification of CD4/CD8 ratio, expression of T cells activation markers and cytokine production). Growth characteristics of human tumors models on humanized mice will be presented either as subcutaneous or as disseminated intravenous model. Randomization parameters were selected regarding both tumor and immune cell sides. Required readouts to understand immune cell modulation (Cell phenotyping and functionality) and related antitumor efficacy will be described. Finally, such models, i.e. humanized NOG mice bearing or not human tumor cells in the context of evaluation of new therapies will be detailed in various pathologies. Citation Format: Caroline Mignard, Jean-Francois Mirjolet, Holger Kissel, Francis Bichat, Olivier Duchamp. Use of humanized NOG mice within the pre-clinical development of new human specific therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1567. doi:10.1158/1538-7445.AM2013-1567