Abstract 624: Humanized mouse models for evaluation of cancer therapies

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.624-624
• Main Authors: Duchamp, Olivier, Bichat, Francis, Mignard, Caroline, Ghiringhelli, François, Mirjolet, Jean-François
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-624

Mice with a humanized immune system, so called “humanized” mouse models, have been established to study the complex interaction of the human immune system during human disorders. In case of cancer research, the in vivo model ideally should recapitulate the biological characteristics of the human tumor and of the related tumor microenvironment in patient such as immune system. Human immune system is reconstituted in immunodeficient mice using either human PBMCs or hematopoietic stem cells (HSCs). Humanized mice bearing human target tumor cells constitute relevant models for evaluation of cancer therapeutics such as bispecific antibodies, immune cell targeting antibodies. In vivo proof of concept studies were performed with humanized mice xenografted with either human disseminated lymphoma or with human solid tumors (tumor cell line and Patient Derived Xenograft model, Her2 positive breast, colon, ovarian and lung cancers) and treated with therapeutic antibodies. Biomarkers of response to immune cell targeting therapies were evaluated by flow cytometry as well as immunohistochemistry analyses. In case of disseminated B-cell lymphoma grafted into mice reconstituted with human PBMC, efficacy of antibody was evidenced by an increased survival and a high decrease of human B cells in mouse bone marrow. Lung and ovarian PDX developed in HSC reconstituted BRGS mice induced an increase in Tregs and a change in T/B ratio in blood and spleen samples. Furthermore, we evidenced the presence of Tregs within human PDX tumor by immunohistochemistry. Citation Format: Olivier Duchamp, Francis Bichat, Caroline Mignard, François Ghiringhelli, Jean-François Mirjolet, IMODI Consortium. Humanized mouse models for evaluation of cancer therapies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 624.