PDX Model Studies
We currently have more than 400 fully characterized proprietary patient-derived xenografts in our portfolio, which represent all major histotypes and tumors, and provide extensive background and characterization.
Patient Derived Xenograft (PDX) Models
Figure 1: Diagram of Patient-Derived Xenograft (PDX) Models
Our PDX Model portfolio includes:
- Subcutaneous, orthotopic, and disseminated models of cancer
- Extensive molecular and pharmacological characterization, and complete records on patients‘ pretreatment
- Integrated approach using the same PDX models and/or the corresponding cell line
- 2D/3D screening assays and subsequent PDX in vivo efficacy studies
- Identification of biomarkers, which predicts tumor sensitivity of compounds
- PDX Model platform using humanized mouse models in standard or single mouse trial (SMT) format
- Zebrafish PDX Tumor Xenograft (ZTX™) Models
- In Vivo Implantable Microdevice PDX Studies; simultaneous in vivo testing of multiple drugs, drug doses, or drug combinations in a single tumor
Constant addition of new PDX models, which are continuously established through international collaborations with major hospitals and universities.
Charles River’s patient-derived xenografts use tumor grafts as explants established as models at low passage numbers (average of six passes removed from patient). They have not been grown in plastic or propagated as cell cultures.
Establishing xenograft tumor models from patient-derived tumor tissue (PDTT) at low passage is believed to conserve original tumor characteristics such as heterogeneous histology, clinical biomolecular signature, malignant phenotypes and genotypes, tumor architecture, and tumor vasculature. Based on this prevalent hypothesis, patient-derived xenografts are believed to offer relevant predictive insights into clinical outcomes when evaluating the efficacy of novel cancer therapies.
By leveraging the wealth of information that we have on each tumor model, we can help you with your study and provide suggested patient-derived xenograft PDX models to test.
Research Director Dr Julia Schueler describes the importance of Patient Derived Xenograft models to aid drug development.
PDX Model Video Transcript
0:00 A PDX model stands for patient-derived xenograft. That means in the oncology space that patient tissue, normally tumor, is transplanted from a human patient into a mouse to maintain as a model. 0:20 In recent years there were multiple efforts to establish and characterize large PDX collections. Although these models are available for a number of decades since the 1980s, their advantages have become more and more important for drug development and tumor biology research. The main advantages of PDX models are that they maintain their genetic heterogeneity as well as the histological makeup of the patient and preserve them over the passages. This gives them the possibility to cover all different histotypes from a specific disease. 0:53 Charles River offers a great PDX collection covering more than 500 different models, including all different entities like the broad models, like non-small cell lung cancer, breast cancer or colon cancer, but as well, tumor models with a high medical need like ovarian cancer, acute myeloid leukemia, non-Hodgkin lymphoma or prostate cancer. 1:17 The PDX models in the Charles River compendium are characterized with molecular techniques like whole-exome sequencing and RNA-seq. We also have patient metadata available as well as histology and immunohistochemistry data and sensitivity toward standard of care treatments. With the advent of new modalities, like for example, immuno-oncology, we tried to enhance our PDX models by analyzing them also in a humanized setting. For example, we analyzed the rates of tumor-infiltrating lymphocytes as well as sensitivity towards checkpoint inhibitors. PDX models are an important part of the preclinical toolbox because they are complementary to the gold standard models like cell line graft models, syngeneic or genetic modified mouse models.
Leveraging In Vitro and Ex Vivo PDX Models
2D and 3D cell-based assays performed with low passage, PDX-derived material serve as cost- and time-effective tools for selecting appropriate PDX models as well as conditions for in vivo efficacy studies. An integrated approach based on PDX in vitro, ex vivo, in vivo, and bioinformatics data will facilitate drug development and enhance the speed of preclinical oncology research.
Pharmacological effects and pharmacokinetics of test compounds can be determined in the tumor microenvironment with high sensitivity and temporal resolution by our in vivo microdialysis services.
Additionally we offer targeted transcriptomics using NanoString gene expression analysis platform to provide information on how therapeutic is regulating the tumor microenvironment.
A High-Content Image Analysis Approach for Quantitative Measurements of Chemosensitivity in Patient-Derived Tumor Microtissues
Learn about the data correlation between in vitro 3D PDX cultures and in vivo PDX tumor models.
Read the Article
To learn more about our offerings, including molecular information, visit our Tumor Model Compendium.
Frequently Asked Questions (FAQs) in Oncology Research
What is a patient-derived xenograft (PDX) model?
Patient-derived xenografts (PDX) are models of cancer where the tissue or cells from a patient’s tumor are implanted into an immunedeficient or humanized mouse. PDX models simulate human tumor biology allowing for natural cancer progression, and offer the most translational research model for evaluating efficacy.
What is a humanized mouse model?
Humanized models are highly immunodeficient mice into which human immune systems are engrafted via peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs). Humanized mice serve as valuable tools for evaluating therapeutic candidates in an in vivo setting relevant to human physiology.
What is a syngeneic mouse model?
Syngeneic mouse models, also known as Allograft mouse tumor systems, consist of tumor tissues derived from the same genetic background as a given mouse strain. As the syngeneic mice retain intact immune systems, they are particularly relevant for studies of immunotherapies.
What is an orthotopic model?
In orthotopic models, tumors are implanted into the equivalent organ from which the cancer originated. Orthotopic models have a similar tumor microenvironment as the original tumor, which allows for the assessment of tumor development in a model that mimics natural disease progression.
What oncology models are right for me?
In a complex and changing field, knowing the next step can be difficult. Answer a few brief questions about your research to receive expert guidance on how to advance your oncology program.