A549 Cell Line Derived Xenograft
Use of the human A549 CDX model is vital for discovery of novel cancer therapeutics. The ability to monitor tumor growth delay in vivo mimics the typical clinical endpoint and is an important estimate of antitumor effectiveness. The A549 subcutaneous CDX mouse model is commonly used in preclinical tumor growth delay studies, including lapatinib as a monotherapy (reduction in angiogenesis), or combination therapies of erlotinib and gefitinib (EGFR-targeted agents).
|Metastatic Models (Lung)||A549|
|Non-Metastatic Models (Lung)||Calu-3, Calu-6, H1155, H460, LL/2, NCI-H1975, NCI-H226|
Proliferating tumor cells invade local tissue, travel through the circulatory system and implant in a foreign tissue. Metastasis leads to high death rates in cancer patients. Cell line derived xenograft (CDX) mouse models are highly utilized in preclinical assessment of novel cancer therapeutics and are a crucial link between initial high-throughput in vitro screening data and anti-tumor efficacy. Metastatic mouse models are utilized to understand the interactions of the anti-metastatic therapeutic and tumor in regards to all organs, bioavailability (e.g. half-life), clearance, immune response and tumor efficacy. Due to the inability to palpate metastatic tumors, the insertion of a luciferase (bioluminescence) or GFP (fluorescence) gene into the genome of the cell line of interest enables the researcher to visually track and quantitate internal tumor progression throughout the in-life portion of the animal study.
A549 is a human adenocarcinomic alveolar basal epithelial cell line that was derived from lung cancer cells. It is commonly used as a model for lung cancer research due to its characteristics, including its ability to grow in culture, its responsiveness to various stimuli, and its similarity to lung cancer cells found in patients. The A549 cell line has been extensively studied and has contributed to a better understanding of lung cancer biology, including the mechanisms of cancer cell growth and invasion, drug resistance, and tumor microenvironment interactions. Researchers also use the A549 cell line to test the efficacy of various cancer treatments, such as chemotherapy, radiation therapy, and targeted therapy. The A549 cell line has been used in numerous studies related to lung cancer, and the knowledge gained from these studies has helped to advance our understanding of this disease and develop new treatments.
What is a Xenograft?
Development of an anti-cancer therapeutic requires intense, well planned studies that follow a streamlined path for success. Primary studies are performed in an in vitro setting that allows for high throughput screening and analysis of multiple compounds of interest. This method enables a focused compound screening approach of multiple cell lines within a specific cancer type, or a divergent approach across a broad range of cancer types. Ultimately, in vitro screening results need to be confirmed in an animal model due to in vitro inadequacies of cells cultured on plastic, as this method is far removed from the microenvironment of a tumor.
As the logical next step in therapeutic development is the administration of the test compound in a living animal, a cell line derived xenograft model (CDX) is created by inoculating human cancer cell lines in test animals. The injected cell lines grow into established tumors, thus, permitting efficacy studies of the test compounds. An alternative to CDX models is the patient derived tumor xenograft (PDX) which consists of implanting human tumor fragments directly in a mouse model. The PDX model avoids concerns with the CDX model since the tumor is never grown on plastic and there is no selection for single cell populations. In contrary to CDX models, the ideology of PDX models is to maintain the cell population, structure and stroma of the initial tumor.
Why use Xenograft Models?
Cell line derived xenograft (CDX) models or patient derived tumor xenograft (PDX) models enable a larger realm of parameters to be studied not capable with in vitro studies. The complete animal system model expands the scope of studies available to include the effect of test compounds on pharmacokinetics (PK), pharmacodynamics (PD), alternate routes of delivery, inhibition of metastasis, CBCs, dosing regimens, dose levels, etc. However, one of the major drawbacks of CDX and PDX models is that the human cancer cell lines or human patient derived tumors must be implanted in immunocompromised mice in order to bypass the graft versus host rejection by the animal. With the increasing focus of the immune systems role in the recognition and elimination of tumor cells (i.e. immunotherapy), major consideration must be taken into account during experimental concept design of the limitation of checkpoint inhibitors or desired immune response involvement in tumor efficacy. Similarly, any tumor regression after treatment with a test compound in these models will not exhibit the potential complement cascade or innate immune response of the injected therapeutic in humans.
What we offer?
Our in vivo xenograft service department evaluates the efficacy of preclinical and clinical cancer therapeutics utilizing more than 90 validated immunocompromised xenograft mouse models. The value of utilizing our xenograft service department is highlighted by the ability to completely characterize the efficacy, dose regimen, dose levels and optimal combination ratios of lead compounds for cancer, obesity, diabetes, infections and immunology research.
During the design and execution of the xenograft study, our scientists will communicate with and assist the client’s decisions regarding these details:
- Study Group Formation: classification of mice by body weight, tumor size or other parameters
- Cancer Cell Line: use of in-house cell lines or utilization of customer-provided cell lines
- Tumor Implantation: intraperitoneal, subcutaneous, submuscular or intravenous
- Test Compound Administration: intraperitoneal, intravenous, tail vein, subcutaneous, topical, oral gavage, osmotic pumps or subcutaneous drug pellets
- Sample Collection: Tumors/tissues can be fixed in 10% NBF, frozen in liquid N2 or stabilized in RNAlater; blood chemistry analysis can be performed throughout the in-life portion of study
Our vivarium is designed such that it enables cost-effective and first-rate preclinical effectiveness testing services. All animal handling and maintenance is regulated following IACUC guidelines. Our facility consists of the following:
- IACUC-regulated and GLP-compliant
- Controlled, limited access lab areas
- Disposable cages
- Sterile food and water
- SPF (specific pathogen-free) animals to guarantee pathogens do not interfere with the experiment
- Established animal handling and micro-injection equipment systems, including an animal health observation program
- All studies follow pre-approved SOPs
Our staff understands that each proposed study design is unique and customized to the client’s needs. We also recognize the importance of the delivered results as being confidential, highly reproducible and that 100% of the intellectual property (IP) is owned by the client.
In order to receive a quote for your xenograft study, email us the specific details listed below in order to efficiently begin the study quote process:
- Cancer cell line(s) used in the study
- Number (n=) of animals in each study group
- Number of study groups and control groups
- Tumor implantation route
- Administration route of test compound
- Species of immunocompromised mouse (e.g. NOD/SCID, athymic Nude)
- Treatment and dose schedule
- Study endpoint and analysis (e.g. tumor growth delay, PK/PD, survival, toxicity, drug combinations)
- Samples collected: tumor and tissues to be collected, including storage condition (e.g. snap frozen, RNAlater, 10% NBF, nucleic acid isolation)