Abstract
BackgroundImmunocompetent animal models are required to study tumor-host interactions, immunotherapy, and immunotherapeutic combinations, however the currently available immunocompetent lung cancer models have substantial limitations. While orthotopic models potentially help fill this gap, the utility of these models has been limited by the very small number of murine lung cancer cell lines capable of forming orthotopic tumors in immunocompetent C57BL/6 hosts.MethodsPrimary lung tumors with specific genetic alterations were created in C57BL/6 background mice. These tumors were then passaged through other animals to increase tumorigenicity and select for the ability to grow in a non-self animal. Once tumors demonstrated growth in a non-self host, cell lines were established. Successful cell lines were evaluated for the ability to produce orthotopic lung tumors in immunocompetent hosts.ResultsWe produced six murine lung cancer lines capable of orthotopic lung tumor formation in immunocompetent C57BL/6 animals. These lines demonstrate the expected genetic alterations based on their primary tumor genetics.ConclusionsThese novel cell lines will be useful for evaluating tumor-host interactions, the impact of specific oncogenic alterations on the tumor microenvironment, and immunotherapeutic approaches. This method of generating murine lines capable of orthotopic growth can likely be applied to other tumors and will broaden the applicability of pre-clinical testing of immunotherapeutic treatment regimens.
Highlights
Immunocompetent animal models are required to study tumor-host interactions, immunotherapy, and immunotherapeutic combinations, the currently available immunocompetent lung cancer models have substantial limitations
Orthotopic systems where tumor cells are directly injected into the lungs of recipient mice can be used to model tumor-host interactions. While this better models metastatic disease and allows for significantly shorter studies genetically engineered mouse models (GEMMs) [7], this approach has been limited by the small number of transplantable murine lung cancer cell lines
The Lewis Lung Carcinoma (LLC) line was subcloned from a spontaneous lung tumor in 1951 [8, 9] while CMT167 was sub cloned for metastatic potential from the CMT64 line derived from a spontaneous lung tumor in 1976 [10, 11]
Summary
Immunocompetent animal models are required to study tumor-host interactions, immunotherapy, and immunotherapeutic combinations, the currently available immunocompetent lung cancer models have substantial limitations. While orthotopic models potentially help fill this gap, the utility of these models has been limited by the very small number of murine lung cancer cell lines capable of forming orthotopic tumors in immuno‐ competent C57BL/6 hosts. Orthotopic systems where tumor cells are directly injected into the lungs of recipient mice can be used to model tumor-host interactions. While this better models metastatic disease and allows for significantly shorter studies GEMMs [7], this approach has been limited by the small number of transplantable murine lung cancer cell lines. To the best of our knowledge, there are only two commercially available C57BL/6 derived murine lung tumor lines capable of forming orthotopic lung tumors in immunocompetent hosts. The development of lines capable of orthotopic growth in a C57BL/6 host is critical as many genetic tools for manipulating the murine immune system in vivo exist in this background
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