 Tumor Xenograft Modeling and Cancer Research
Comparative Biosciences, Inc. provides state-of-the-art preclinical xenograft models in multiple species and with multiple cell lines to support preclinical research and assessment of anticancer drugs.
Our expert scientific staff possess strong industrial and academic backgrounds. With our new and complete laboratory facilities, validated xenograft models and supporting studies, Comparative Biosciences, Inc. is able to support a complete discovery and development program for anti-cancer drugs.
Scientific Staff
- Carol Meschter, DVM, PhD, DACVP; CEO, Board Certified Pathologist
- James Christenson, PhD; Vice President, Expert in drug development and animal modeling
- Harry Ruan, PhD; Director of Preclinical Research, Expert in Pharmacology/Toxicology and Cancer Biology
- Poonam Kuruganti, PhD; Manager Histology, Expert in immunohistochemistry, FACS, molecular biology and neuroscience
Comparative Biosciences, Inc. offers tumor studies in a variety of species, a wide range of routes of administration, and is experienced with many classes of therapeutic agents. Detailed descriptions of our major capabilities follows.
- Human Xenograft Implants
- Species
- Routes of Administration
- Common Study Endpoints
- Classes of Therapeutic Agents
- Supporting Capabilities
- Pharmacokinetic Studies including radiolabeling
- Toxicity Studies
- Clinical Pathology and FACS
- Histopathology
- Immunosuppression
- In Vivo Laboratory Facilities and Equipment
Human Xenograft Implants
 Validated Tumor Cell Lines at Comparative Biosciences, Inc.
- Breast: MDA MB-231, MCF-7, MDA-MB-435
- Colon: Caco-2, HCT-116, COL 205, L5174T Carconoma
- Lung: A549, LS174T, Lewis Lung (syngeneic)
- Prostate: LNCAP, PC-3, DU-145
- Melanoma: B16F0, B16F10 (syngeneic)
- Ovarian: SK-OV-3
- CNS: U87-MG
- Myeloid: Daudi
- Pancreatic: PANC-I, PANC-II
- Other ATCC lines and custom lines upon request
Validation of Xenograft Studies
Typical Study Parameters
- Human tumor cells grown in culture (CBI Cell Bank, ATCC or custom lines)
- Cell/tissue implant subcutaneously (interscapular, flank, mammary fat pads) into immunocompromised animals
- Tumors measured during growth phase
- Animals treated with vehicle, test article, and positive controls
- Various protocol-specified parameters/markers assessed
- Report preparation
Syngeneic Implants
- Immunocompetent rodents are implanted with tumor cells from the same species
- Lewis Lung Carcinoma, B16F0, B16F10
- Tumors measured during growth phase
- Animals treated with vehicle, test article, and positive controls
- Various protocol specified parameters assessed
- Report preparation
 Metastatic Cell Lines
- Certain tumor lines readily metastasize
- Metastases may be measured or counted
- Metastatic lines LS174T, MCF-7, A549 well established
- Tumors and metastases measured in vivo using chemiluminescence-based imaging technology
- Animals treated with vehicle, test article, and a positive control
- Various protocol-specified parameters/markers assessed
- Report preparation
OrthotopicTumor Studies
- Tumor cells are implanted surgically at target sites
- Pancreas (PANC-II)
- Prostate (PC-3)
- Colon (LS174T)
- Tumors and metastases measured in vivo using chemiluminescence-based imaging technology
- Animals treated with vehicle, test article, and positive control
- Various protocol specified parameters/markers assessed
- Report preparation
Angiogenesis and Neovascularization
- Mechanism of Angiogenesis critical area of cancer research
- Neovascularization of tumor, metastases, implants, corneal implants may be assessed
- Fluorescent angiography
- Histopathology
- Immunohistochemistry
- Immunofluorescence
- Knockout and transgenic mice with vascular defects available
- Corneal Micropocket in Mice and Rats
 Rat Corneal Micropocket
The study and development of anti-angiogenic therapies depends on reliable and reproducible stimulation models of neovascular response. The corneal micropocket provides a robust and rapid assay for assessing neovascular response in the cornea.
- Ocular pellet preparation with varying basic fibroblast growth factor (bFGF) concentrations, which is adjusted for specific study requirements
- Pellet is surgically implanted into the base of the corneal micropocket
- Histologic examination records neovascularization in the cornea using a slit lamp microscope connected to a camera
- Intravital fluorescent angiography is conducted
- Pharmacokinetics of aqueous or vitreous
- Histopathology and immunohistochemistry
Species
In addition to regular immunocompetent animals (rodents, rabbits and dogs), CBI offers studies with:
- Nude and SCID mice
- Athymic rats
- Irradiated or immunosuppressed rodents
- Knock out and transgenic mice
- Rat corneal micropocket
- Rabbit corneal micropocket
 Routes of Administration
Standard Routes: Oral, intravenous, subcutaneous, intraperitoneal, intramuscular. Also:
- Topical or local
- Short term or continuous infusion
- Ocular: Topical, Intraocular or intravitreal
- Combination routes
- Intraorgan or surgical delivery
- Alzet Pump delivery
- Intracranial delivery via stereotaxic injection or infusion in mice and rats
Common Study Endpoints
- Tumors and metastases measured in vivo using chemiluminescence-based imaging technology
- Rate of tumor growth or tumor delay
- Metastasis or metastatic growth rate
- Mortality
- Histopathologic end points
- Immunohistochemistry endpoints
Classes of Therapeutic Agents
Comparative Biosciences, Inc. is skilled with many classes of therapeutic agents including:
- Traditional cytotoxic agents
- Anti-neoplastic agents
- Monoclonal antibodies
- Anti-angiogenesis agents
- Immune system stimulators
- Cancer vaccines
- Drug delivery and targeting systems
- Gene therapy systems
- Non-traditional anti-cancer agents
- Radiolabeled therapeutic agents
 Supporting Capabilities
In addition to conducting the actual xenograft studies, Comparative Biosciences, Inc. also provides a range of supporting capabilities, including pharmacokinetics, radiolabeled studies, acute and subacute toxicity studies, clinical pathology, histopathology, immunohistochemistry, and immunosuppression.
- Pharmacokinetics including radiolabeling
- Maximum tolerated dose, acute and subacute toxicity
- Hematology and clinical chemistry
- Histopathology including GLP toxicologic pathology
- Immunohistochemistry, immunfluorescense, in situ hybridization
- Antibody Cross Reactivity Studies (research and GLP)
- Immunosuppression
Pharmacokinetic Studies including radiolabeling
- PK/PD critical components of early preclinical drug development.
- Single dose, multi-dose, and infusion PK
- Multiple species: Small animals, immunocompromized rodents, rabbits, and dogs
- Plasma, serum, aqueous, vitreous, CSF, organs
- Small molecule, biologics and radiolabeled
- Bioanalytical-HPLC, LCMS, LCMS/MS, radio counting available
- GLP and NonGLPRadiolabeled studies may facilitate targeting and tumor specificity
- Radiolabeling may be part of a tumor pharmacokinetic assessment or may be an integral part of the therapeutic process
- Licensed for 14C, 3H, 131I, 125I, 92Y, others upon request
- Counting and analysis available
Toxicity Studies
Simple toxicity studies assist in assessment of anti-cancer agents and support PK and xenograft studies.
- Acute toxicity studies
- Simple MTD and Step-up Step Down
- Short and long term multiple dose studies
- Identification of target organs
- Clinical chemistry and hematology determinations
- May be conducted as separate studies or parameters may be incorporated into efficacy studies
Clinical Pathology and FACS
- Hematology and coagulation
- Clinical Chemistry
- Cell Sorting and FACS Analysis
- GLP and non-GLP
 Histopathology
Histopathology is a powerful tool in the assessment of anti-cancer agents.
- Complete necropsy, organ weights, clinical chemistry
- Routine paraffin sectioning and special stains
- Cryotomy and Immunohistochemistry including:
| TUNEL |
Transferrin |
Angiogenesis |
| PCNA |
CD31, CD34 |
Isolectins |
- In Situ Hybridization, Fluorescent Angiography, Plastics
- Antibody Cross Reactivity
- Digital Image Analysis
- ACVP Board Certified Veterinary Pathologist
- GLP and nonGLP
Immunosuppression
Immunosuppression may be induced by cyclophosphamide, Cesium irradiation, and combinations
- Verification of neutropenia or leukopenia by hematologic assessment
- Blood analyzers calibrated by species
- Complete Blood Count including white cell count with differential, hemoglobin, red blood cell count, hematocrit, Wintrobe parameters, and platelet count to verify immunosuppression
- Immunocytological assessments of bone marrow, spleen, lymphoid organs, thymus
- FACS analysis of cellular subsets
In Vivo Laboratory Facilities and Equipment
 Special air handling- Microisolator and ventilated racks
- Laminar flow hoods in rooms
- Liquid nitrogen cell storage tank
- Incubators
- Inverted Phase Microscope
- Multi-headed teaching microscope
- -20 and -80C Freezers
- Fundoscope
- Kowa Small Animal Fundus Angiography Camera
- Slit Lamp
- Digital Image Analysis and Histomorphometry Software
- USDA Registered and Inspected
- FDA Registered and Inspected
- OLAW Assurance
- Compliance with NIH Guide
Histology laboratory facilities and equipment
- 4,000 sq ft. state-of-the-art Histopathology Lab
- Automated slide and cassette labelers
- VIP processors
- Embedding stations
- Automated microtomes
- Cryotomes
- Automated stainer
- Complete paraffin, immunohistochemistry, fluorescence, in situ, megasections,
and plastics/resin/grinding capabilities
- ACVP Board Certified Pathologists
- Computerized Pathology Data Acquistion Systems
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