Transcript Xenograft Services PPT
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Xenograft
Benefits of Xenograft
Develop new therapeutic agents quickly, efficiently and cost effectively Evaluate the efficacy and toxicity of potential therapeutic agents www.signalsblog.ca
Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another.
Evaluate target compound activity using
in vivo
system (human cells) Predict cytotoxicity of cancer drugs
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected] • 512.433.6177
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Xenograft
The Gold Standard in Oncology
In vivo
xenograft efficacy evaluations remain the gold standard and the workhorse of oncology preclinical research.
Xenograft models combine the advantages of working with human cancers with the physiological relevance of an
in vivo
host.
Typically, immunodeficient mice serve as hosts for a wide variety of human tumors, effectively serving as proxies for human subjects.
Xenograft models remain a mainstay in oncology research, playing a key role in drug discovery and development.
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
Services >
Xenograft
Assay Pipelines
Pipeline Xenograft Assay I
We design your experiment based on your project requirements. Through years of experience and literature search we guarantee optimal experimental setup according to selection of mice stain, cell lines, inoculation and dosage.
Pipeline Assay II - test a compound
You send us a compound and cell line to establish xenograft. We establish xenograft animal models and test compound activity and how it affects tumor growth in an established xenograft model.
Pipeline Xenograft Assay III - test a cell line
You send us a cell line and we test it’s ability to establish tumor growth in standard immunodeficient mice.
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
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Xenograft
Experimental Objectives of Compound Testing
How does the test compound affect tumor growth? Does the test compound inhibit tumor invasion or metastasis? Localization of test compound in the tumor?
Define drug characteristics:
Bioavailability Toxicity Efficacy Potency Is cell line tumorigenic? Changes in gene expression upon treatment or gene manipulation
ParamHow does gene manipulation in a cell line affect following parameters:
Tumor growth , Invasiveness, Metastasis
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
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Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
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Xenograft
Basic Study Design
Xenograft studies can be designed to identify lead compounds, optimize dose schedules, and identify combination strategies.
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
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Xenograft
Service Options
Use in-house or customer-provided cell lines or tumor Begin testing a compound immediately after injecting mice with tumor cells (unstaged) or once the tumors reach a certain size (staged) Assign mice to groups randomly or stratify them by body weight, tumor size, disease factors, or any combination of parameters Administer test compounds by any of the following methods: topically, IP, IV, SC, PO, high pressure tail vein, osmotic minipumps (SC or IP), SC drug pellets, or in the food or water Snap freeze harvested tumors or fix them for histology or other specialized assays Analyze blood chemistry at various times throughout the study
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
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Xenograft
Sample of Cell Lines Maintained at Altogen Labs
Cell Line Organ Disease
A549 Lung Carcinoma DU145 Prostate Carcinoma PC3 LNCaP Prostate Prostate Adenocarcinoma Carcinoma MDA-MB-231 FaDu Caki -1 Caki - 2 PANC-1 SK-MEL-2 SK-OV-3 U-87 MG A431 SW-480 HeLa Breast Pharynx Kidney Kidney Pancreas Skin Ovary Brain Epidermis Colon Cervix Adenocarcinoma Squamous carcinoma Clear Cell Carcinoma Clear Cell Carcinoma Epithiloid Carcinoma Malignant Melanoma Adenocarcinoma Glioblastoma/ Astrocytoma Epidermoid Carcinoma Adenocarcinoma Adenocarcinoma
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
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Xenograft
Growth rates for different cell lines
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
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Xenograft
Administration Options
Route of dose:
Intratumoral Intramuscular Oral Intravenous Intratracheal Subcutaneous Intraperitoneal
Frequency of dose Duration of dose
www.patient-derived-xenograft-services.com
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
Services >
Xenograft
Endpoints
Estimated tumor volume (L x W 2 /2) Mean/median time to specified tumor volume Survival time to specified tumor volume Tumor doubling time Tumor growth inhibition (TGI) Tumor growth delay (TGD) Increased life span (ILS) Tumor cell kill rate
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177
Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics
Services >
Xenograft
Additional Analysis Options
Clinical observations every day Haematology analysis (blood cell count) Clinical chemistry profile (of urine and plasma) Evaluate the degree of metastasis. Characterization of the tumor (necrosis, etc) The tumor is divided and preserved for further analysis Cryo-preservation (for cell culture) Formalin fixed tumors and tissues (for histopathological and immunostaining analysis) RNAlater fixed tumors and tissues (for RNA and DNA isolation, and gene expression analysis)
Altogen Labs • 4020 S Industrial Dr • Suite 130 • Austin • TX • 78744 • USA [email protected]
• 512.433.6177