Abstract 3116: Developing engineered and primary cancer cell lines for oncology drug development

Abstract

Abstract Cancer cell lines are effective in vitro systems in oncology drug development. The success of many targeted cancer drugs benefited from the utilization of cancer cell lines such as ones from American Type Culture Collection (ATCC) and Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ). Recent multiplatform omics research revealed complex diversity of cancers, many of which were classified into subtypes that have distinct genomic signatures, show different prognosis patterns, and may respond differently to same drug treatment. For example, colorectal cancers were separated into four consensus molecular subtypes, and subtype 1 is marked by high microsatellite instability and has worse survival after relapse1. Cancer subtypes may not be well represented in existing cell line libraries. Immortal cell lines for some cancers, such as soft-tissue sarcoma2, may also be rare. It is therefore pertinent to expand current cell line collection, a common approach being to establish primary cell lines directly from cancer patients, preferably with complete clinical information. In addition, current library may also lack of cell lines with rare mutations that exist at low frequency in naïve patient tumors and frequently occur under drug treatment. For example, Erlotinib—a first generation of EGFR inhibitor—induces the EGFR T790M mutation, and Tagrisso—a third generation of EGFR inhibitor—induces the EGFR C797S mutation. It is desirable to create engineered lung cancer cell line with both mutations. An engineered cell line with both mutations can be more efficient in developing EGFR inhibitors overcome the resistance of both mutations. In this study, we report the establishment and characterization of over 120 engineered cell lines and several dozens of primary cell lines across multiple cancers. For the engineered cell lines, we used CRIPSR technology to create cell lines bearing specific mutation for well-studied target proteins such as EGFR, FLT3, ELM4-ALK. In addition, we also created cell lines that may be used for immunotherapy development targeting PD-1, PD-L1, TIM3, OX40, etc. We used Sanger sequencing, flow cytometry, cell viability assay, in vitro and in vivo efficacy studies to validate and characterize the cell lines. To make the resources easily accessible to researchers, we created a searchable database named InnopediaTM that presents detailed information of the engineered and primary cell lines. Access is open with registration. The database also provides comprehensive genomic and efficacy data, retrieved from published research, for over 1000 conventional cell lines.