Abstract 5671: Humanized mouse models for evaluation of cancer therapies

Abstract

Abstract Mice with a humanized immune system, so called “humanized” mouse models, can be used to study the complex interactions between the human immune system and tumor cells. In order to assess compounds efficiency in immune-oncology, the in vivo model should recapitulate the biological characteristics of the human tumor and the related immune microenvironment. The choice of mouse strain is the first critical factor as genetically engineered mouse strains differentially express cytokines and growth factors. Then the choice of human antigen/target to be assessed drives the choice of the tumor models and the immune population to be transferred into mice. We developed on different immunodeficient mouse strains multiple humanization strategies using either human PBMCs, Hematopoietic Stem Cells (HSCs), or specific human immune cells such as Dendritic Cells (DCs), T cells, subset of T cells (e.g. gamma9 delta2 T cells) and NK cells. We also developed mouse humanization models using combinations of immune subpopulations such as co-transfer of autologous T cells and DCs.Humanized models were then used for in vivo proof of concept studies with mice xenografted with cell lines (human disseminated lymphoma, orthotopic/subcutaneous solid tumors) or patient-derived xenografts. Tumor-bearing humanized mice were treated with cancer therapeutics such as bispecific antibodies, ADCC-inducing antibodies, Treg targeting antibodies, TLR agonists, vaccines and adoptive T cells transfer therapeutic antibodies. Therapeutics efficiency was assessed by following up mice survival and tumor growth. The impact of therapeutics on tumors and immune cells was also assessed by flow cytometry and immunohistochemistry analyses. In case of disseminated lymphoma and ovarian human tumor in mice reconstituted with human PBMCs, significant antitumor activity of bispecific antibodies were evidenced by an increase in survival, decrease in specific biomarkers (CA125 for ovary) and decrease of residual disease. Citation Format: Jean-Francois Mirjolet, Josselin Caradec, Olivier Duchamp, Francis Bichat, Caroline Mignard. Humanized mouse models for evaluation of cancer therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5671.