Development of murine tumor homograft panels and their genetic fingerprints for their identification to ensure the quality controlled I/O studies using these models

Mouse tumors of homografts in the corresponding syngeneic mouse strains have become the key experimental system in immune-oncology (I/O) research and evaluating mouse surrogate I/O therapies. There are several types of mouse tumor homografts, including syngeneic cell line-derived, spontaneous or carcinogen-induced tumor-derived, or tumorigeneic GEMM (genetic engineered mouse model) -derived. We have created an increasingly larger panel of such diverse murine tumor homografts (now u003e 40 syngeneic cell line-derived and u003e 60 GEMM primary tumor-derived, or MuPrime®, usually driven by defined activated oncogenes frequently seen in human cancers) to support global I/O researches, including discovery of new drugs or drug targets, discovery/validation of biomarkers of both predictive and pharmacodynamic (PD) natures, as well as mechanism of actions (MOA). We are also systematically characterizing these heterogeneous library of murine tumors, in terms of genomic (Transcriptome-sequencing, or RNAseq), immunological (TILs and cytokine profiles), histopathological (lung, PDAC, breast, prostate, liver, CRC, bladder, kidney carcinoma, lymphoma, melanoma, sarcoma, leukemia, etc), growth and pharmacological (SOC, I/O) profiles. With the broad applications of these models at different laboratories and different times, it is prudent to track and QC the tumor to ensure their absolute correct identification (ID) by a readily routine assay. Unlike human-originated tumors (e.g. xenografts), either cancer cell line-derived or patient tumor-derived (PDX) whose genetic ID can readily be tracked by STR (short tandem repeat) genotyping or HLA tissue typing, murine tumors come from limited strains of inbred experimental mice, thus lack of sufficient genetic and/or tissue diversity to be used, in a readily performed assay, for individual murine model ID. To this end, we have established a novel efficient model quality control and tumor ID method in murine tumor model systems, in which we sought out to identify unique gene features in each individual murine tumor among a cohort of u003e 100. We have validated many such unique gene features in the original cell lines or primary tumors and/or their subsequent passages. Our results demonstrated that these unique gene features can served as genetic fingerprints for murine model ID. Citation Format: Jie Cai, Wubin Qian, Bin Fan, Xiaobo Chen, Sheng Guo, Davy Ouyang, Wenqing Yang, Annie An, Jinglei Bi, Dongliang Mo, Henry Li. Development of murine tumor homograft panels and their genetic fingerprints for their identification to ensure the quality controlled I/O studies using these models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5116.