Abstract 1156: New spontaneous and carcinogen-induced mouse-derived isograft (MDI) tumor models for immune therapeutic approaches

Abstract

Abstract First findings in the late 1990s and the early 2000s, that blockade of immune checkpoint inhibitors (ICI) by antibodies could induce rejection of established tumors and induce immunity also to secondary exposure with these tumor cells, led again to a stronger focus of experimental studies on syngeneic tumor models in immunocompetent animals. The availability of such models, however, is mainly limited by the small number of genetically-modified (GEM) or long-term passaged cell line-derived tumor models. We here describe establishment and first characterization of a new type of animal tumor models, named Mouse-Derived-Isografts (MDI), from spontaneously appearing or carcinogen-induced syngeneic tumors in both sexes of various mouse strains (C3H/HeN, CBA/J, BALB/C, DBA/2N and C57BL/6N). The tumors were obtained from animals during long-term observation (≥ 1-2 years) of normally fed, otherwise untreated animals (spontaneous - sMDI) or during short-term observation (3-9 month) of once subcutaneously, intramuscularly, intraperitoneally or orally methylcholanthrene (MCA) or methyl-nitroso-urea (MNU) treated animals (carcinogen - cMDI). Criteria to perform a primary necropsy were critical weight loss, bad general conditions or externally observable tumor growth in monitored animals. At this first step, tissues were assessed only macroscopically, and conspicuous ones were transplanted (in PDX-like manner) as small pieces into sex-matched syngeneic animals. If possible tissue/tumor pieces were also frozen and stored in 10% DMSO freezing medium at -80°C. In a second step these re-transplanted, outgrowing tumors were amplified once again in syngeneic mice for freeze storing, and then the models were finally established by re-transplantation and testing outgrowth of the frozen stored tumor pieces in the syngeneic animals. The tumors appear phenotypically stable, as far as routine standard HE stained sections could show. General characteristics of these models are; they are primary spontaneous or carcinogen-induced tumors, of low passage number (<10), propagated as tissue pieces only in mice without tissue culturing, and thus with conserved original tumor characteristics as assessed microscopically and intra-tumoral immune cell populations analyzed by flow cytometry. Citation Format: Peter Jantscheff, Janette Beshay, Thomas Lemarchand, Cynthia Obodozie, Christoph Schaechtele, Holger Weber. New spontaneous and carcinogen-induced mouse-derived isograft (MDI) tumor models for 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 1156.