Abstract
Abstract Background: Humanized mice are a promising translational research model for evaluation of pharmacological compounds efficacy and safety in Oncology. Their use has been enhanced by the development of new stocks of immunodeficient hosts, most notably mouse strain such as NOD-scid/IL2rγ null mice (NSG). As previously described (L. Schultz et al, J. Immunol. 2005) the NSG mice could also be successfully humanized after engraftment of human hematopoietic stem cells (HSC). NSG mice have also been shown to be superior to other immunodeficient mice (BALB/c nu/nu, NOD/Shi-scid) for xenograft of tumour material. These models are particularly needed in preclinical development where there is no appropriate small animal model combining the human immune system and human tumour. Methods: Freshly collected umbilical cord blood (UCB) samples were provided by the “établissement français du sang, EFS” following the French ethical rules. The UCB were selected for their HSC CD34+ content and T cells depleted before being intracardiacally injected in whole body irradiated newborn NSG mice. The reconstitution of a human immune system within mouse was analyzed in peripheral blood and in primary and secondary lymphoid organs (bone marrow, spleen and thymus) using a 7-color FACS analysis. The mice were then xenografted with tumour cell lines, fresh primary human solid tumours and haematological malignancies to combine the development of human cancer and human immune system within the same mouse. Results and conclusions: Fifteen weeks after stem cells injection, the peripheral blood contains about 50% of human leukocytes distributed as followed: about 50% of T lymphocytes, about 40% of B lymphocytes, about few percent of monocytes, macrophages, granulocytes, natural killer cells and platelets. At same time, the central chimerism within lymphoid organs for human leucocytes has represented about 80%, 85% and 95% in bone marrow, spleen and thymus cells, respectively. This NSG mouse model opens new in vivo perspectives to study the complex relationships between the human immune system and human tumour cells under therapeutic treatments with biologics (antibody-dependent cell-mediated cytotoxicity, antitumour vaccination strategies . . .). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 394.
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