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Pharmacological and pharmacodynamic test for PDX tumor model

2016-05-30 17:13:39.0

Our PDX (Patient-Derived Xenograft) platform is a direct patient-derived tumor model established in B-NDG mice with severe immune deficiency. In this model, fresh tumor cells or patient tissues are transplanted into B-NDG mice to make the human tumor grow and amplify in a low-rejection host environment. The newly built tumor model also reserves the high-heterogeneity that is characteristic of patient tumor tissue, and partial medium compositions of the tumor microenvironment are also preserved. The PDX model has no in vitro culture stage compared with the traditional tumor cell line model, which provides an environment closer to patient’s tumor tissue. By utilizing this kind of tumor model, the tumorigenesis mechanism can be studied more in depth. The pharmacological and pharmacodynamic reaction of the drug in the patient’s tumor tissue can be studied to find potential therapeutic targets, providing a tumor model with a high translational medicine value for tumor drug development.

In recent ten years, the wide application of the PDX model has shown that it has very good application prospects for tumor drug preclinical evaluation and clinical efficacy prediction. The pharmacodynamic effect of anti-cancer drugs on large-scale PDX models reflects the results of clinical applications in patients. Determining the preclinical pharmacodynamic effects of new anti-cancer drugs by utilizing PDX models can therefore provide a deeper evaluation of a new drug’s clinical application potential.

PDX model development with B-NDG mice is superior to model development with other immune-deficient animals due to tumor formation rate and modeling speed, which provides guarantee for further development and application of the PDX model. B-NDG mice are excellent host animals for immune humanization, and other innovative tumor models can be built for tumor translational medicine.


·Service contents

1. Individualized PDX modeling service

Develop in vivo models for clinical tumor specimens using B-NDG mice as host animals. For tumor models that are hard to establish in other immune-deficient animals, PDX model efficiency can be improved by using B-NDG mice’s severe immune deficiency.

Available services: The clinical tumor specimen selected by the customer is quickly inoculated into B-NDG mice after tumor collection. Methods such as subcutaneous vaccination, kidney capsule inoculation, and orthotopic implantation can be used to provide customers with custom PDX modeling service.


2. PDX model molecular subtyping

Deep sequencing for a target gene in the succesful PDX model specimen; about 1000 types of tumor-related genes can be analyzed, and detailed tumor classification can be performed by combining other biomolecular analysis methods. PDX models will be selected for tumor and anti-cancer drug R & D according to the original tumor specimen and the corresponding PDX model’s classified characteristics.

Available services: Provide database and subsequent analysis methods to assist customers in selecting the appropriate tumor model based on the molecular subtyping results of the PDX model. Further specific experimental analysis and comparison can be performed for the PDX model by including the customer’s specific analysis requirements.


3. Pharmacological and pharmacodynamic research with the PDX model

In vivo pharmacological and pharmacodynamic evaluation for tumor drugs in the PDX tumor model is widely applied by tumor drug R & D researchers for the preclinical assessment. By combining the specific drug research and development plan, the corresponding PDX tumor model can be used as the main working model for in vivo pharmacological and pharmacodynamic evaluation. The required pharmacological test plan can be completed based on this model, and the data from the preclinical animal can be used to sufficiently prove the in vivo pharmacodynamic results, thereby promoting clinical drug development.

Available services: The PDX tumor model selected by customers will be used to complete in vivo pharmacological and pharmacodynamic tests. These tests will prove the dose-effect relation and relevant pharmacological mechanism of the tumor drug. They will also provide the test analysis description for the PK/PD relationship, as well as other pharmacodynamic test evidence based on the tumor model.


4. Preclinical pharmacodynamic test of large-scale PDX model (mouse trial)

Tumor heterogeneity is an important characteristic of PDX model that makes it a superior test model in comparison to the traditional cell line model. The PDX model can maintain patient tumor tissue characteristics to more closely resemble the patient’s original tumor, therefore making the PDX model a better test platform for tumor drug pharmacodynamic evaluation. Large-scale PDX models are more abundant in tumor heterogeneity. Each PDX model can serve as a single patient’s tumor, thereby sufficiently representing the different tumor characteristics of the patient population. Performing pharmacodynamic determination for new tumor drugs in multiple PDX models can therefore significantly show the drug’s curative effect in specific patients. Mouse trials can be performed for these tests by making a single PDX tumor represent a single patient.

Available services: Provide the corresponding PDX model for the tumor-drug’s target clinical subtypes; provide customers with mouse trials with large-scale models to determine the new drug’s possible clinical reaction in a patient population; provide scientific R & D schemes for further clinical research based on the preclinical research results, thereby saving on R & D costs.


5. Research of a PDX model base molecular target and corresponding biomarkers

Establishment of a PDX tumor model with high tumor heterogeneity can become the basis for an in vivo tumor model that can aid in biomarker development. Analyses such as sequencing equimolecular analysis and pharmacodynamics test phenotype analysis can be performed for possible drug R & D targets and biomarker development in the model base. Specific PDX tumor models are selected to meet the specific needs of drug R & D, and can also provide important guidance for clinical drug development. For example: biomarker identification is performed by comparing the reaction of the PDX models to the drug, which can identify the tumor model that is sensitive to the drug and therefore an appropriate subject of pharmacodynamic tests. The biomarker identified in the PDX model can further guide the drug’s clinical development, since it can select the effective patient population and obtain clinical pharmacodynamic results as soon as possible.

Available services: Provide customers with large-scale PDX models for in vivo target verification and biomarker development. The target or biomarker can be compared and proven via multiple analyses.

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