Transcript Xenograft Services PPT

Provider of Global Contract Research Services
Accelerating Preclinical Research, Drug Discovery & Therapeutics
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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
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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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Provider of Global Contract Research Services
Accelerating Preclinical Research, Drug Discovery & Therapeutics
Services >
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
Services >
Xenograft
Experimental Objectives of Compound Testing
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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
www.skyepharma.com
Provider of Global Contract Research Services
Accelerating Preclinical Research, Drug Discovery & Therapeutics
Services >
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
Services >
Xenograft
Service Options
 Use in-house or customer-provided cell lines or tumor
 Begin testing a compound immediately after injecting mice with tumor cells
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(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
Xenograft
Sample of Cell Lines Maintained at Altogen Labs
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Cell Line
A549
DU145
PC3
LNCaP
MDA-MB-231
FaDu
Caki -1
Caki - 2
PANC-1
SK-MEL-2
SK-OV-3
U-87 MG
A431
SW-480
HeLa
Organ
Lung
Prostate
Prostate
Prostate
Breast
Pharynx
Kidney
Kidney
Pancreas
Skin
Ovary
Brain
Epidermis
Colon
Cervix
Disease
Carcinoma
Carcinoma
Adenocarcinoma
Carcinoma
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
Services > Xenograft
Growth rates for different cell lines
Provider of Global Contract Research Services
Accelerating Preclinical Research, Drug Discovery & Therapeutics
Services >
Xenograft
Administration Options
 Route of dose:
Intratumoral
 Intramuscular
 Oral
 Intravenous
 Intratracheal
 Subcutaneous
 Intraperitoneal
 Frequency of dose
 Duration of dose
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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 W2 /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
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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