Abstract 1325: Evaluation of immuno-oncology related treatment in syngenic and human reconstituted immune systems

Abstract

Abstract Immunotherapy based on monoclonal antibodies targeting cancer cells is now developed as a valid approach to treat cancer. Modulation of novel immune checkpoints and other targets are highly promising approaches against cancer and many other diseases. They have the potential to activate the immune system and to establish an active defense against pathological conditions. In addition, antibodies, antibody fragments, and other biologics can also have a strong impact on the immune system which needs to be evaluated early on. In order to develop and accurately evaluate these immunology linked approaches, appropriate preclinical models with relevant immunological readouts are needed at different stages of therapy development. Ideally, methods should be available that allow predictive readouts in vivo and ex vivo. A comprehensive panel of tools was constructed and validated aiming at evaluating the modulation of the immune system by new therapies. In immunocompetent mice, immune cells were studied for the detection of their cell surface markers, induction of proliferative phenotype, antigen-specific T lymphocyte detection, secretion of soluble mediators using FACS phenotyping, cytometric bead assay (CBA) or Luminex multiplex technologies and ELISPOT. We report on a panel of syngenic tumor models (4T1, B16-F10, CT26, EMT6, AY27, LLC1, MBT-2 and Renca) our capacity to correlate subpopulation of immune infiltrating cells (as T cells, macrophages, NK cells, granulocytic and monocytic cells) and the therapeutic effects of critical antibodies directed against Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death 1 membrane protein (PD-1). In immunodeficient mice, the reconstitution of the mature human immune system with PBMC or naïve human immune system using hematopoietic stem cells was used to evaluate the modulation of those immune cells by therapies through human cytokine release and onset of graft versus host disease. All of these tools were used in the context either of rodent syngenic models or humanized mouse models. In addition to their use in immune system modulating anti-cancer therapies, these humanized or syngenic models also have a potential application in many other therapeutic areas such as autoimmune diseases, inflammation, anti-infectives. Citation Format: Marc Hillairet de Boisferon, Francis Bichat, Caroline Mignard, Xavier Tizon, Damien France, Jean-François Mirjolet. Evaluation of immuno-oncology related treatment in syngenic and human reconstituted immune systems. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1325. doi:10.1158/1538-7445.AM2015-1325