Abstract 5683: Value of new spontaneous and carcinogen-induced mouse-derived isograft (MDI) tumor models for drug development of novel immune therapeutic approaches

Abstract Checkpoint inhibitor treatment has already become a common therapy of various cancer types. However, there is still a growing need for well-characterized preclinical mouse models, as clinical data indicate that patients only partially respond to this regiment. Currently, cell lines cultured from the 1970s are used frequently to evaluate novel therapies. In a research development program, new mouse-derived isografts (MDI) were established from spontaneously occurring and carcinogen-induced tumors. These tumors are transplanted as tissue pieces in a PDX-like manner and tested for their solid growth. Furthermore, the efficacy of immune checkpoint inhibitor treatment is evaluated and the presence of different immune cell populations in the tumor is characterized by FACS analysis. In addition, RNA-seq data complete the first characterization of these models and will give insights into the expression level and genetic modification of genes in these models. Here, the spontaneous MDI model JA-0009 and two carcinogen-induced MDI models JA-2042 and JA-2011 are presented. Whereas JA-0009 and JA-2011 tumors are only partially affected by immune checkpoint inhibitor treatment, JA-2042 shows a significant response in a combined treatment of anti-PD-1/anti-CTLA-4. Characterization of the infiltrated immune populations revealed a high number of T cells, especially Treg cells. In contrast, the JA-0009 tumor is infiltrated mainly by macrophages of M2 type with a low number of CD8+ T cells and the JA-2011 tumor by neutrophils. Taken together, the new MDI models complement the existing GEMs and cell-line derived syngeneic tumor models by their new properties (low passage number, no tissue culture, conserved original tumor properties and intra-tumoral immune cell populations) to characterize novel immune-modulatory agents in drug development. Citation Format: Janette Beshay, Peter Jantscheff, Cynthia Obodozie, Christoph Schaechtele, Holger Weber. Value of new spontaneous and carcinogen-induced mouse-derived isograft (MDI) tumor models for drug development of novel immune therapeutic approaches [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 5683.