Abstract 1562: Choosing the right preclinical model for cancer immunotherapy: The “SyngenOmic” toolbox..

Recent FDA approvals of ipilimumab and sipuleucel-T for the treatment of metastatic melanoma and castrate-resistant prostate cancer respectively have validated the approach to modulate the immune system for the clinical treatment of cancer. MedImmune Oncology, has an extensive pipeline and expertise in investigational Immune Mediated Therapy in Cancer (IMT-C) drugs (e.g. tremelimumab and MEDI4736), and is heavily invested in this novel era of cancer therapeutics. Pre-clinical assessment of the validity of potential IMT-C drugs can be enabled by the use of syngeneic tumours established in immuno-competent animals. MedImmune9s pharmacology team has lead efforts to develop such models, to a point that a panel of 15 different validated syngeneic tumour types is available in house for studies to progress projects. The intention of selecting relevant models and of minimizing animal experimentation, reduces the number of models tested for each project, and allows for detailed genetic and proteomic characterization of treatment dependent effects within our models. Utilising both in vitro and in vivo approaches, we have generated transcriptomic and genomic data for our cell lines, the resulting implanted tumours and for the relevant lymphatic organs (draining lymph node and spleen). Using key proteomic/cell markers through IHC and FACS analysis, we are also evaluating the immune profile/status of our tumour bearing animals in parallel. Finally, in order to establish the disease relevance and prognostic value of our models we are analyzing our cell panel for the presence of somatic mutations in 50 genes previously implicated in human cancers. Once completed, the resulting dataset will hopefully help pre-clinical scientists to refine their in vivo plans and deliver more clinically-relevant pharmacology packages for the progression of cancer immunotherapy drug candidates. Citation Format: James A. Harper, John Prime, Athula Herath, Jane Howell, Marianna Papaspyridonos, Amy Popple, Judith Anderton, Michelle Morrow, Arthur Lewis, Liz Henley, Matthew McCourt, Richard Sainson. Choosing the right preclinical model for cancer immunotherapy: The “SyngenOmic” toolbox. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1562. doi:10.1158/1538-7445.AM2013-1562