Abstract A38: IMODI initiative: a novel holistic and integrative approach with patient-derived tumor models
Authors: VACON Francoise LE , Arnould Laurent , Bruno Alain , Calvet Loreley , Colombel Marc , Corre Jill , Cuvillier Olivier , Eckel Benedicte , Forraz Nico , Gonzalez-Jouhanneaud Alexandra , Guenot Dominique , Iovanna Juan , Kuras Mariana , Lautrette Christophe , Malavaud Bernard , Merle Philippe , Meyer-Losic Florence , Praz Francoise , Rosmorduc Olivier , Sarry Jean-Emmanuel , Tabone Severine , Vaglio Philippe , Ysebaert Loic , Duchamp Olivier 
Published: March 2017

Many reports support that xenografts from patient-derived xenografts in mice or rat recapitulate well the molecular diversity, cellular heterogeneity, and histology seen in patient tumors. However, several lacks such as the limited clinical diversity of the PDXs, the absence of influence of human microbiome, the absence of human drug metabolism and the reduced immune system are limiting the predictive values of these PDX models. To set-up a holistic integration of these criticisms, we have associated efforts from public hospitals, academic groups, biotechs and private pharmaceutical companies with the financial support of the French Ministry of Industry.

First, to improve the clinical diversity of the PDX collections, surgical specimens or biopsies from patients with 8 different types of cancers (lung, breast, ovary, pancreas, liver, prostate, AML, myeloma) are collected since 2013 to establish large collections of PDXs in mice. In addition, primary cultures of cells from these samples are established leading to a collection of cell lines from the stroma and the tumoral compartment. The established models are being evaluated for ex vivo and in vivo sensitivities to relevant anticancer drugs, histological and molecular characteristics. All model characteristics are being compiled in a web-based database for efficient features search and interconnection.

Second, to improve our knowledge on the role of the human microbiote, feces and feeding habits are collected from patients with cancer and from mice with PDXs before and after treatment allowing a comparison of the microbiote profiles. In order to mimic the human drug metabolism, we are generating mice with humanized liver showing distinct drug pharmacokinetic profiles from the ones observed in parental mice. Finally, humanization of the immune system in mice is developed by several approaches including the use of induced pluripotent stem cells from cancer patients.

We will present the first models characterized and will discuss their usefulness and chance to bring benefit to patients via this holistic strategy developed within IMODI initiative.

Citation Format: Francoise LE VACON, Laurent Arnould, Alain Bruno, Loreley Calvet, Marc Colombel, Jill Corre, Olivier Cuvillier, Benedicte Eckel, Nico Forraz, Alexandra Gonzalez-Jouhanneaud, Dominique Guenot, Juan Iovanna, Mariana Kuras, Christophe Lautrette, Bernard Malavaud, Philippe Merle, Florence Meyer-Losic, Francoise Praz, Olivier Rosmorduc, Jean-Emmanuel Sarry, Severine Tabone, Philippe Vaglio, Loic Ysebaert, Olivier Duchamp. IMODI initiative: a novel holistic and integrative approach with patient-derived tumor models. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A38.