Tumor Models

Cancer is a serious public health concern with well over one million new diagnoses annually in the US alone. Cancer kills one in four Americans, and is second only to cardiovascular disease as the most common cause of death. Treatment for most cancers is insufficient despite early detection methods. As a result, there is an urgent need for novel anti-cancer agents. Biomodels provides cost-effective outsourcing for a wide spectrum of in vivo and in vitro preclinical oncology models, designed specifically to enable the successful translation of novel anticancer drugs, biologics and devices into human clinical trials. 

As members of the American Association for Cancer Research (AACR), our Oncology Group has presented their own work at AACR-sponsored conferences, published in top journals, and have made significant contributions to translational cancer research. Our uniquely personal approach to our clients’ needs recognizes that the goals of different companies of various sizes and in different stages are not the same.  Our focus on providing clinically recapitulative models comes with significant experience and validation data in including co-modeling of clinical chemo/radio/immunotherapy standards of care as benchmarks or as combination therapies with new potential therapeutics.

Oncology Models Overview
Tumor Models Description Endpoints
Syngeneic Cells are from the same species as  host and are immunocompatible therefore immunocompetent animals can be used

In Vivo:

  • Survival
  • Tumor volume; Quantitative
  • Luminescence/Fluorescence (IVIS)
  • Metastasis
  • Histology
  • Cytokine Induction
  • Protein/RNA Expression; Immunophenotyping, 
  • Limiting Dilution Tumor Initiation

 

In Vitro:

  • Tumorsphere Formation
  • Viability/Proliferation
  • Anchorage Independent Growth
  • Invasion/Migration
  • Wound Healing
  • FACS Profiling
Xenograft Tumor cells are implanted subcutaneously in rats or mice
Orthotopic Cells are implanted directly into the desired organ site in rats or mice
Metastasis After seeding at primary orthotopic or heterotopic site, primary tumors can be resected if necessary and metastasis/tumor dissemination assayed in fluorescent/bioluminescent reporter-expressing tumor cells (including PDX)
PDX Patient derived xenograft (PDX) lines are recently derived from patients and passaged exclusively in vivo, maintaining many characteristics of the parental tumor, including histological, gene expression, copy number profiles and heterogeneity.  For these reasons, PDX models may be superior to traditional cell lines
Germ-Free & Gnotobiotic Oncology models performed under germ-free/gnotobiotic or specific pathogen free conditions are employed to assay the effects of microbiome on carcinogenesis, cancer growth/progression/dissemination and/or response to treatment
In Vitro Assays Assays for: Proliferation and survival, migration and invasion, tumorspheres/colony formation, and FACS biomarker analysis
Other Models Transgenic/Humanized, Genetically Engineered, Chemically Induced, Cancer Stem Cells
*Several models are compatible with IVIS imaging for in-life monitoring of disease progression

 

 

Murine/Rat Cancer Cell Lines Validated In Vivo

Indication Cell Lines Readouts
Blood Cancers A20, EL4, L1210
  • Survival
  • Tumor growth kinetics (caliper/IVIS)
  • Progression/metastasis kinetics
  •  Weight change
  • Immunohistochemistry
  •  Immunophenotypic analysis (flow)
  • Gene expression (WB, qPCR)
  • Cytokine analysis (ELISA, qPCR etc.)
  • Mixed Lymphocyte reactions
  •  Adoptive transfer
  • In vitro assays
Breast Cancer

4T1, Walker 256 (rat), *4T1-Luc

Colorectal Cancer CT-26
Brain Cancer

GL261, F98 (rat), *GL261-Luc

Lung Cancer LLC-1
Melanoma B16.F0, B16.F10, B16.F10.SIY
Sarcoma Yoshida
Treatments: Chemotherapies, Radiotherapies, Immunotherapies

*Indicates Bioluminescent Cell Lines

 

 

Human Cancer Cell Lines Validated In Vivo

Indication Cell Lines Readouts
Blood Cancers

CCRF-CEM, CEM, Daudi, Jeko-1, Jurkat, Kasumi-1, KG-1, Molt-4, Raji, Ramos, Reh, RPMI8226, THP-1, Z-138

  • Survival
  • Tumor growth kinetics (caliper/IVIS)
  • Progression/metastasis kinetics
  •  Weight change
  • Immunohistochemistry
  •  Immunophenotypic analysis (flow)
  • Gene expression (WB, qPCR)
  • Cytokine analysis (ELISA, qPCR etc.)
  • Mixed Lymphocyte reactions
  •  Adoptive transfer
  • In vitro assays

Breast Cancer

MDA-MB-231, MDA-MB-468, *HBCx-14-Luc1, *MDA-MB-231-Luc

Colorectal Cancer HCT-15, HCT-116, HT-29, *HCT-116-Luc, *HT-29-Luc
Brain Cancer

IMR-32, U87-MG, U118-MG

Head and Neck Cancer Cal-27, FaDu, SCC-25, SCC-154, *FaDu-Luc, *SCC-25-Luc
Liver Cancer HepG2, Hep3B
Lung Cancer A549, H69, H82, H460, H520, H1299, H146, *H460-Luc
Melanoma SK-MEL-28, *SK-MEL-28-Luc, *MELx-006-Luc1
Ovarian Cancer OVCAR-3, *OVA21-DMT-Luc
Pancreatic Cancer AsPC-1, BxPC3, MIA PaCa-2, Panc-1
Prostate Cancer DU-145, PC-3
Renal Cancer 786-0, A498
Stomach Cancer N-87
Treatments: Chemotherapies, Radiotherapies, Immunotherapies*Indicates Bioluminescent Cell Lines

*Indicates Bioluminescent Cell Lines

Syngeneic

Syngeneic models provide the advantage of studying the interaction between the immune system and the tumor because the cells are from the same species as the host. Biomodels regularly conducts a wide spectrum of subcutaneous and orthotopic syngeneic models, co-modeled with common checkpoint inhibitor mAb therapies, and translatable endpoints for immunotherapies, such as mAb therapies, cell-based therapies, vaccination therapies etc. Additionally, Biomodels’ germ-free/gnotobiotic facility and enhanced handling protocols can be used to validate novel immunotherapies that work via modulation of commensal microbiota. Finally, Biomodels has significant expertise in many common ex-vivo immune assays including Immunophenotyping of tumor-infiltration/systemic leukocyte populations, MLR assays, multiplex ELISAs, histology, and a variety of biomarker analyses.

Syngeneic Tumor Models:

Indication Murine/Rat Cancer Cell Lines Readouts
Blood Cancers A20, EL4, L1210, *L1210-Luc
  • Survival
  • Tumor growth kinetics (caliper/IVIS)
  • Progression/metastasis kinetics
  • Weight change
  • Immunohistochemistry
  • Immunophenotypic analysis (flow)
  • Gene expression (WB, qPCR)
  • Cytokine analysis (ELISA, qPCR etc.)
  • Mixed Lymphocyte reactions
  • Adoptive transfer
  • In vitro assays
Breast Cancer 4T1, Walker 256 (rat), *4T1-Luc
Colorectal Cancer CT-26
Brain Cancer GL261, F98 (rat), *GL261-Luc
Lung Cancer LLC-1
Melanoma B16.F0, B16.F10, B16.F10.SIY, *B16.F10-Luc
In Vitro Assays Assays for: Proliferation and survival, migration and invasion, tumorspheres/colony formation, and FACS biomarker analysis
Sarcoma Yoshida
Treatments: Chemotherapies, Radiotherapies, Immunotherapies

*Indicates Bioluminescent Cell Lines

 

 

Mice sourced from different vendors were handled under specific-pathogen free (SPF) handling protocols and murine melanoma cells seeded as subcutaneous allografts in mice to assess the contributions of microbiome to the relative efficacy of immune checkpoint inhibition on tumor growth.
Murine glioblastoma cells expressing a bioluminescent reporter were seeded intracranially in allogeneic mice. Standard of care chemo/radiotherapy was applied and tumor response assayed by IVIS imaging.
Xenograft

Subcutaneous injection of tumor cells in mice and rats offers a relatively simple and efficient tumor model system to test the efficacy of potential therapeutics for the treatment of cancer.  Xenograft models are additionally useful in addressing the presence of drug-related toxicities. We offer a wide variety of classical and patient derived (PDX) tumor cell lines which can be studied as xenografts in both mice and rats. Experimental endpoints for xenograft studies include: tumor volume, histology, cytokine induction, protein, and RNA expression.  Various humanized xenograft models are also available to serve therapeutic paradigms that rely on the interplay of human tissues/systems/genetics with human tumors in a murine model.

Xenograft Tumor Models

Indication Human Cancer Cell Lines
Blood Cancer CCRF-CEM, CEM, Daudi, Jeko-1, Jurkat, Kasumi-1, KG-1, Molt-4, Raji, Ramos, Reh, RPMI8226, THP-1, Z-138
Breast Cancer MDA-MB-231, MDA-MB-468, *HBCx-14-Luc1, *MDA-MB-231-Luc
Colorectal Cancer HCT-15, HCT-116, HT-29, CaCo-2, *HCT-116-Luc, *HT-29-Luc
Brain Cancer IMR-32, U87-MG, U118-MG

Head and Neck Cancer

Cal-27, FaDu, SCC-25, SCC-154, *FaDu-Luc, *SCC-25-Luc

Melanoma

SK-MEL-28, *SK-MEL-28-Luc, *MELx-006-Luc1

Ovarian Cancer

OVCAR-3, *OVA21-DMT-Luc

Pancreatic Cancer

AsPC-1, BxPC3, MIA PaCa-2, Panc-1, *PANx-005-Luc1, *BxPC3-Luc

Prostate Cancer

DU-145, PC-3

Renal Cancer

786-0, A498

Stomach Cancer

N-87

Liver Cancer

HepG2, Hep3B

Lung Cancer

A549, H69, H82, H460, H520, H1299, H146, *H460-Luc
Treatments: Chemotherapies, Radiotherapies, Immunotherapies
Readouts: Survival, Tumor growth kinetics (caliper/IVIS), Progression/metastasis kinetics, Weight change, Immunohistochemistry, Immunophenotypic analysis (flow), Gene expression (WB, qPCR, Cytokine analysis (ELISA, qPCR etc.), Mixed Lymphocyte reactions, Adoptive transfer, In vitro assays*Indicates Bioluminescent Cell Lines

*Indicates Bioluminescent Cell Lines
 

 

Orthotopic/Heterotopic

Subcutaneous xenograft models of cancer can be useful in evaluating the potential of a novel therapy; however, many aspects of tumor growth and dissemination are more accurately modeled following implantation into the corresponding tissue of origin, or into tissue corresponding to a frequent site of metastatic dissemination. For these reasons, orthotopic/heterotopic models tend to be more clinically relevant and better predictors of drug efficacy. Biomodels has substantial expertise in orthotopic implantation and tumor growth and dissemination following tumor cell inoculation into a large number of orthotopic and heterotopic tissue contexts, including those that assess therapies targeting the role of non-transformed tumor associated stromal cells. These efforts are aided by our noninvasive in-life imaging capabilities using the IVIS Lumina III system and our abilities to transduce cell lines to express bioluminescent/fluorescent reporters. 

Orthotopic Tumor Models

Indication Human Cancer Cell Lines Murine/Rat Cancer Cell Lines Readouts
Blood Cancer

 

*L1210-Luc
  • Survival
  • Tumor growth kinetics (caliper/IVIS)
  • Progression/metastasis kinetics
  • Weight change
  • Immunohistochemistry
  • Immunophenotypic analysis (flow)
  • Gene expression (WB, qPCR)
  • Cytokine analysis (ELISA, qPCR etc.)
  • Mixed Lymphocyte reactions
  • Adoptive transfer
  • In vitro assays
Breast Cancer MDA-MB-231, MDA-MB-468, *MDA-MB-231-Luc *4T1-Luc
Colorectal Cancer

 

CT-26
Brain Cancer U87-MG F98(rat), *GL261-Luc

Head and Neck Cancer

Cal-27, FaDu, SCC-25, SCC-154, *FaDu-Luc, *SCC-25-Luc

 

Liver Cancer

HepG2, Hep3B

 

Lung Cancer

H460-Luc LLC-1

Melanoma

SK-MEL-28, *SK-MEL-28-Luc B16.F0, B16.F10, B16.F10.SIY

Pancreatic Cancer

*PANx-005-Luc1, BxPC3, *BxPC3-Luc

 

Treatments: Chemotherapies, Radiotherapies, Targeted therapies.

*Indicates Bioluminescent Cell Lines
 

 

Immune-compromised mice were seeded with human squamous cell carcinoma lines into the tongue and standard of care schedule of fractionated radiotherapy was applied.  Tumor response was assayed by IVIS imaging.
Representative IVIS images over time for the orthotopic tongue human squamous cell carcinoma model
Metastasis

Metastatic dissemination of cancer cells from a primary tumor to new organs is the primary cause of cancer-related mortality.  While recent research has elucidated metastatic mechanisms, exposing new potential targets and intervention strategies, novel therapies remain desperately needed for advanced stage metastatic cancers.  Newer models, including those utilizing metastatic tumor cells stably expressing bioluminescent or fluorescent reporters and seeded at the orthotopic site allow for high resolution tracking of metastasis as a quantifiable readout in a mechanistically relevant context.

Metastatic Tumor Models

Indication Human Cancer Cell Lines Murine/Rat Cancer Cell Lines Readouts
Blood Cancer

 

*L1210-Luc
  • Survival
  • Tumor growth kinetics (caliper/IVIS)
  • Progression/metastasis kinetics
  •  Weight change
  • Immunohistochemistry
  •  Immunophenotypic analysis (flow)
  • Gene expression (WB, qPCR)
  • Cytokine analysis (ELISA, qPCR etc.)
  • Mixed Lymphocyte reactions
  •  Adoptive transfer
  • In vitro assays

Breast Cancer *MDA-MB-231-Luc, *HBCx-14-Luc1 *4T1-Luc
Colorectal Cancer *HCT-116-Luc, *HT-29-Luc

 

Brain Cancer

 

*GL261-Luc

Melanoma

*SK-MEL-28-Luc *B16.F10-Luc

Pancreatic Cancer

*BxPC3-Luc

 

Treatments: Chemotherapies, Radiotherapies, Targeted therapies.

*Indicates Bioluminescent Cell Lines
 

 

A patient derived (PDX) triple-negative breast cancer expressing a bioluminescent reporter is seeded at the orthotopic site in immune-compromised mice.  When tumors reach a specified volume, the primary tumors are resected in survival surgeries and standard of care and/or novel experimental therapies can be assayed in clinically recapitulative adjuvant or neoadjuvant settings.  Metastatic progression can be quantified at high resolution by in-life imaging (IVIS).
Representative images from the animals/groups above showing the animals bearing the primary tumor, as well as metastatic dissemination of bioluminescent PDX breast cancer following primary tumor resection
Heterotopic Xenograft
Patient-Derived Xenograft (PDX)

Patient-derived xenograft are recently derived from patients and are propagated exclusively in-vivo, preserving many characteristics of the patient tumor including heterogeneity, copy number, gene expression and histological profiles.  For these reasons, PDX models are considered to be more accurate models than traditional cancer cell lines grown in monolayers on plastic.  PDX lines are well characterized and additional patient information is also often available.  PDX lines transduced in suspension with bioluminescent reporters allow for in-life tracking tumor growth and dissemination from accurate orthotopic contexts.

PDX Tumor Models

Indication Human Cancer Cell Lines Readouts
Breast Cancer *HBCx-14-Luc1, *HBCx-5-Luc2, *HBCx-6-Luc, *HBCx-12B-Luc3
  • Survival
  • Tumor growth kinetics (caliper/IVIS)
  • Progression/metastasis kinetics
  •  Weight change
  • Immunohistochemistry
  •  Immunophenotypic analysis (flow)
  • Gene expression (WB, qPCR)
  • Cytokine analysis (ELISA, qPCR etc.)
  • Mixed Lymphocyte reactions
  •  Adoptive transfer
  • In vitro assays

Melanoma *MELx-006-Luc1
Ovarian Cancer *OVA21-DMT-Luc
Pancreatic Cancer *PANx-005-Luc1, *TPAN1-IFA-Luc, *PANC2-SAL-Luc

Prostate Cancer

*PAC120-Luc
Treatments: Chemotherapies, Radiotherapies, Immunotherapies*Indicates Bioluminescent Cell Lines

*Indicates Bioluminescent Cell Lines

 

 

A patient derived pancreatic cancer PDX expressing a bioluminescent reporter was seeded at the orthotopic site in immune-compromised animals, and standard of care chemotherapy or experimental treatments were administered.  Tumor growth and progression was monitored by in-life imaging (IVIS).
Germ-Free and Gnotobiotic

Commensal or pathogenic microbes function in close association with our immune system and are increasingly appreciated as important mediators of antitumor immunity and response to immunomodulatory cancer treatment modalities.  Germ-free, gnotobiotic or specific-pathogen free oncology models provide elegant systems for efficacy testing of novel cancer therapies that function via rational modulation of the microbiome. 

JAX SPF v TAC SPF B16F10SIY PDL1 Relative response of a subcutaneous murine melanoma to immune checkpoint inhibition was assayed in genetically identical mice housed and handled under specific pathogen free protocols and derived from different vendors, previously shown to possess compositionally dissimilar microbiomes.
In Vitro Assays

In our primary screening program, compounds can be quickly tested for their ability to inhibit tumor growth and invasive migration in cultured cells. Biomodels can also examine the impact of test compounds on tumorspheres/colony formation, co-modeling with tumor stroma and other tissues relevant to tumor growth and dissemination. We are equipped with cell separation/FACS capabilities for further analysis of cell populations and drug response.  

  • Growth/Proliferation
  • Survival/TUNEL
  • Invasion/Migration
  • Anchorage Independent Growth
  • Cell separation
  • Flow-cytometry based assays
  • RNA/Protein analysis (WB, multiplex ELISA, qPCR, immunocytochemistry)
Subscribe to RSS - Tumor Models