The emerging class of novel drugs, including targeted biologics, shows compelling efficacy in oncology. The ability to test new agents, alone or in combination, in predictive human disease models supports the identification, optimization and application of new therapeutic strategies. Human primary cell-based BioMAP® Systems are designed to recapitulate the complex signals and phenotypic responses of diseased tissues and thus provide broad biological coverage of multiple and diverse indications. The BioMAP Diversity Plus panel consists of 12 systems with combinations of human primary endothelial cells, blood leukocytes, macrophages, bronchial epithelial cells, smooth muscle cells, fibroblasts, and keratinocytes relevant for inflammation, oncology and fibrosis. BioMAP Systems are capable of detecting and distinguishing activities of a very broad range of mechanistically diverse compound classes. We have generated a proprietary reference database of BioMAP profiles of >4,500 bioactive agents (drugs, biologics, experimental and environmental chemicals) and employ proprietary software and data mining tools for classification and similarity analyses of bioactivity profiles. The activities captured in the BioMAP profile are consistent with biological activities observed in patients.
We have recently expanded the platform to include tumor microenvironment model systems to interrogate the phenotypic impact of compounds on inflammation, immune-function, tissue-matrix remodeling/metastasis, vascular/angiogenesis and/or tumor biology. BioMAP oncology systems consist of co-cultures of human primary fibroblasts (stromal) or endothelial cells (vascular) and PBMC (immune) with the HT29 (CRC) or NCI-H1299 cell lines (NSCLC) to model the inflamed host-tumor stromal and vascular microenvironments, respectively. Profiling clinical and development checkpoint modulators including antibodies, small molecules and combinations resulted in increased immune-related activity as measured by the resulting cytokine profile and cell markers of immune modulation, consistent both with the levels of CTLA4 in the system and with clinical results from patients. BioMAP® Systems thus provide a highly useful platform to (1) identify anti-inflammatory and anti-cancer effects of various agents and combinations and (2) identify different phenotypic outcomes of these agents that influence disease progression and resolution. Together these BioMAP data will support the discovery and development of safer and more effective therapies.
Citation Format: Alison O'Mahony, Jason Ptacek, Jennifer Melrose, Karen Matta, Ellen Berg. Profiling compounds in human primary cell BioMAP® systems for drug discovery and development in cancer immunotherapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B134.
- ©2016 American Association for Cancer Research.