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Aragen Bioscience offers a diverse range of preclinical oncology models and services with client-specific customized study design. These include human xenograft tumor models as well as the more complex sub-renal capsule, patient-derived xenograft (PDX), and syngeneic tumor models. We monitor PK/PD correlations using plasma/serum following test article administration, tumor response, changes in tumor volume and weight, as well as studying genomic, proteomic and metabolomic biomarkers.

Xenograft models are extensively used in investigational new drug (IND)-enabling studies for evaluation of new chemical entities (NCEs) and new biological entities (NBEs) as potential anticancer agents. Our scientists have developed and validated numerous xenograft models in Ncr Nu/Nu, NOD-SCID and SCID-Beige mice. We will also customize and utilize human cell lines of your interest to conduct in vivo proof of concept studies. Syngeneic models enable testing anticancer agents in an immunocompetent system, although they may not entirely reflect the human immune competency. With intact immune system, syngeneic models are pertinent for evaluating immunologically based targeted therapies alone or in combination.

We have expertise and facilities to support your pre-clinical oncology research with our extensive range of in vivo models enlisted below:

Human Cell lines @ Aragen Bioscience (USA/India)
S.No Cell line Origin of Tumor Species USA IND
1 A431 Epidermoid carcinoma Human Y Y
2 Hep G2.2.15 Hepatocellular carcinoma Human Y
3 A-673, A-673-Fluc Rhabdomyosarcoma (Ewing tumor) Human Y
4 KASUMI-1 Acute myeloid leukaemia Human Y Y
5 MV4-11 Beta myelomonocytic leukemia Human Y
6 NALM-6 B-Cell leukemia Human Y
7 SUDHL-10 B-Cell leukemia Human Y
8 MDA-MB-468 Breast cancer Human Y
9 MDA-MB-231, MDA-MB-231-Fluc Breast cancer Human Y Y
10 MCF-7, MCF-7-Fluc Breast cancer Human Y
11 SK-Br-3 Breast cancer Human Y
12 Raji, Raji-Fluc-GFP Burkitt’s lymphoma Human Y
13 FaDu Cervical carcinoma Human Y
14 HT-29 Colon adenocarcinoma Human Y
15 HCT-116, HCT-116-Luc Colon adenocarcinoma Human Y
16 Colo 205 Colon adenocarcinoma Human Y
17 SW480 Colon adenocarcinoma Human Y
18 KM-12 Colon adenocarcinoma Human Y
19 MKN-1-Fluc Gastric cancer Human Y
20 U87-MG, U87-MG-Fluc Glioblastoma Human Y
21 Hep 3B Hepatocellular carcinoma Human Y
22 PLC/PRF/5 Hepatoma Human Y
23 A549, A549-Fluc-GFP Lung cancer (NSCLC) Human Y
24 NCI-H460 Large cell lung carcinoma Human Y
25 NCI-H226 Lung cancer (NSCLC) Human Y
26 H1299 Lung cancer (NSCLC) Human Y
27 NCI-H358 Lung cancer (NSCLC) Human Y
28 NCI-H1944 Lung cancer (NSCLC) Human Y
29 NCI-H1573 Lung adenocarcinoma Human Y
30 Calu-6 Lung anaplastic carcinoma Human Y
31 NCI-H292 Mucoepidermoid pulmonary carcinoma Human Y
32 A427 Lung carcinoma Human Y
33 A375 Melanoma Human Y
34 KG-1 Multiple myeloma Human Y
35 NCI-H929 Multiple myeloma Human Y
36 U266 Multiple myeloma Human Y
37 MM1.S Multiple myeloma Human Y
38 RPMI8226 Multiple myeloma Human Y
39 WSU-DLCL-2* Non-Hodgkin’s lymphoma Human Y
40 IGROV-1* Ovarian cancer Human Y Y
41 SK-OV-3, SK-OV-3-Fluc Ovarian cancer Human Y
42 A2780 Ovarian cancer Human
43 OVCAR-3 Ovarian adenocarcinoma Human Y Y
44 OV90 Ovarian cancer Human Y
45 PANC-01 Pancreatic cancer Human Y
46 AsPC-1 Pancreatic cancer Human Y
47 BxPC3, BxPC3-Fluc-GFP Pancreatic cancer Human Y
48 PANC.10.05 Pancreatic cancer Human Y
49 MIA PaCa-2, MIA-PaCa- 2-Rluc Pancreatic cancer Human Y
50 22rv.1 Prostate cancer Human Y
51 LNCaP Prostate cancer Human Y
52 DU-145 Prostate cancer Human Y
53 PC-3 Prostate cancer Human Y Y
54 786-O, 786-O-Fluc Renal cell carcinoma Human Y
55 A498 Renal cell carcinoma Human Y Y
56 Caki-1, Caki-1-Fluc Renal cell carcinoma Human Y
Animal Cell lines @ Aragen Bioscience (USA/India)
S.No Murine Cell Line Origin of Tumor Species USA IND
1 4T1, 4T1-Fluc Breast cancer Mouse Y
2 MC-38, MC-38-Fluc Colon cancer Mouse Y
3 CT-26, CT-26-Fluc Colon cancer Mouse Y
4 B16-F10 Melanoma Mouse Y
5 B16-F1 Melanoma Mouse Y
6 Hepa 1-6 Hepatoma Mouse Y
7 LL/2 Lung cancer Mouse Y
8 A20 Lymphoma Mouse Y
9 EL4 Thymoma Mouse Y
10 E.G7-OVA Ova-expressed thymoma Mouse Y
11 C6VL  T-cell lymphoma Mouse Y
12 L1210 Leukemia Mouse Y
13 Renca Renal cortical adenocarcinoma Mouse Y
14 Ba/F3 a murine interleukin-3 dependent pro-B cell line Mouse Y
15 D17 Osteosarcoma Canine Y
S.No Cell Line Origin of Tumor Type of Model Species USA IND
1 A549-FLuc-GFP Lung cancer (NSCLC) Lung metastasis Human Y
2 BxPC3-FLuc-GFP Pancreatic cancer Orthotopic Human Y
3 Mia Paca-2-RLuc Pancreatic cancer Orthotopic Human Y
4 U87-MG-Luc Glioblastoma Orthotopic Human Y
5 MDA-MB-231-FLuc Breast cancer Orthotopic Human Y
6 SKOV-3-FLuc Ovarian cancer Orthotopic Human Y
7 Raji-FLuc-GFP Burkitt’s lymphoma Disseminated xenograft Human Y
8 4T1-FLuc Breast cancer Lung metastasis Mouse Y
9 GL-261-Luc Glioblastoma Orthotopic Mouse Y
S.No Tissue Type Human Cell Line
1 Leukemia lymphoma Daudi, MV4.11
2 Burkitt’s lymphoma Raji, Raji-Luc-GFP
3 Acute myeloid leukemia Kasumi-1, KG-1
4 B-cell leukemia NALM6, SUDHL-10
5 Multiple myeloma NCI-H929, U266, MM.1s, RPMI-8226
6 Colon adenocarcinoma HT-29, HCT-116, HCT-116 Luc-GFP, Colo 205, SW480
7 Lung cancer (NSCLC) A549, NCI-H226, NCI-H1299, NCI-H358, NCI-H1944, A549-Luc-GFP
8 Lung anaplastic carcinoma Calu-6
9 Lung adenocarcinoma NCI-H1573, NCI-H292, NC-H460
10 Renal cell carcinoma Caki-1, 786-O
11 Hepatocellular carcinoma Hep G2, Hep 3B
12 Pharynx squamous cell carcinoma FaDu
13 Pancreatic cancer BxPC-3, BxPC-3-Luc-GFP, MIA PaCa-2-Luc
14 Ovarian cancer SKOV-3, SKOV-3-Luc, OVCAR-3
15 Prostate cancer LNCaP, LNCaP-Luc, 22rv.1
16 Breast cancer MDA-MB-468, MDA-MB-231, MDA-MB-231-Luc, MCF-7, MCF-7 Luc, BT-474
17 Glioblastoma U-87MG-Luc
18 Melanoma A-375

 

S.No Tissue Type Murine Cell Line
1 Breast cancer 4T1, 4T1-Luc, EMT-6
2 Colon cancer MC-38 , CT-26
3 Melanoma B16-F10, B6-F1
4 Liver cancer Hepa 1-6
5 Lung cancer LL/2
6 Lymphoma A20
7 Thymoma EL4, E. G7-OVA
8 Leukemia L-1210
9 Renal cortical adenocarcinoma Renca

Additional Models

  • Lung metastasis model
  • Orthotopic models of breast, pancreas, and brain
  • Sub-renal capsule assay
  • Vaccine model

Other Oncology Support

  • In vivo bioluminescent imaging
  • 70+ cancer cell lines of validated models stored in-house 
  • Pharmacokinetics and bioavailability of various test materials in tumor-bearing mice
  • Target engagement of compound in tumor tissue and PK/PD correlation
  • Maximum tolerated dose (MTD) studies in immunocompromised mice

Typical readouts are, but not limited to:

  • Tumor growth kinetics
  • Immunophenotyping with multicolor FACS
  • Cytokine panels
  • ELISpot assays
  • Multi-gene analysis
  • Histology/ immunohistochemistry
  • Protein/ peptide analytics

These services cater to a range of therapeutic areas including immuno-oncology research.

Immuno-oncology (IO) and CAR T-Cell Therapeutics Evaluation Capabilities

In recent years, immuno-oncology research has made rapid progress, thanks to new therapeutic options such as CAR T-cell. While the CART therapy is increasingly being used for the treatment of human hematologic malignancies, there are several challenges including targeted delivery, immunogenicity, and efficacy in solid tumors.

To address these challenges and help you expedite your IO research projects to market, we have developed various mouse models to screen potential CAR T-cell therapeutics to support IND-enabling process.

Aragen Bioscience is a leading integrated discovery, development, and manufacturing solutions provider for the global life sciences industry. Our Discovery Biology Services include in vitro and in vivo screening of new immunotherapies, including engineered chimeric antigen receptor (CAR) T-cells using translational animal models to support efficacy studies in xenograft and syngeneic tumor models.

Validated Immuno-oncology Model

MC38 cells represent a widely recognized murine colon adenocarcinoma cell line extensively employed in preclinical investigations, notably within the realm of immuno-oncology. Using the luciferase-tagged MC38 that was developed at Aragen Bioscience, we successfully replicated the effects of anti-PD-1, anti-CTLA-4, and their combination in the subcutaneous MC38 tumor model. In addition, all three standard-of-care chemotherapeutics significantly reduced tumor volume compared to the vehicle group. For the first time, we demonstrated that anti-CTLA-4 alone and in combination with irinotecan prevented subcutaneous MC38 but not B16F10 tumor growth in re-challenged responders, suggesting a specific immunity toward MC38 tumor cells. Our study demonstrated that subcutaneous MC38- Luc tumor model is a robust model for testing multiple drug modalities including immunotherapy and chemotherapy.

Figure 1

Figure 2 Comparative effects of immune checkpoint inhibitors and standard-of-care drugs on MC38 tumor growth.

Figure 3 Effect of treatments on tumor-infiltrating CD4+ T and CD8+ T cells.

Figure 4 MC38 and B16F10 tumor rechallenge in tumor free survivors.

The Aragen Bioscience Advantages

  • Experienced and skilled team of in vivo research scientists to support pre-clinical research from study design through execution.
  • Experience in intravenous transfer of CAR T-cells (or human PBMCs) into a mouse and in vivo ex vivo CART therapeutic evaluations for liquid and solid tumors.
  • Experience in cell line derived xenograft- in humanized mouse models and non-invasive monitoring of tumor progressions in animals.
  • Detection of tumor-specific antigens by flow cytometry, in vitro or in vivo pre-screening of human PBMCs.
  • Same/next day shipment of biological samples from our research facility at Morgan Hill, CA.
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