Background
Mouse xenograft animal models are used to assess the efficacy of medicines before they are tested in clinical trials. They are primarily used for screenings and drug development for cancer, diabetes, infections, obesity, immunology, and inflammation research. Xenograft models offer fast testing of novel compounds on well characterized cancer cell lines. Commercial tumor cell lines, or even patient-derived xenograft-derived cell lines can be injected into mice models to determine how effective potential cancer drugs/therapies are in vivo. Cytotoxicity of drugs, antibody therapies, viral therapies, and more can all be evaluated with this method. Results are usually available within 30-40 days following tumor cell injection (xenotransplantation). There are hundreds of tumorigenic cancer cell lines available for xenograft studies for a wide variety of cancer types (see ATCC or DSMZ for details on tumorigenic cell lines). Cancer cell lines have a wealth of information associated with them including tumor suppressor gene status, gene expression profiles, biomarker expression, and growth factor requirements that give the researcher a choice to find a cell that meets their specific needs (the largest selection of xenograft models is commercially available at Altogen Labs).
Recent research by Meehan et al. used human xenograft models on immunocompromised mice to replicate human physiology for diseases and infections. They cultured human subcutaneous fat first in vitro before implanting into the mice. The transplants were put on the mice’s ear pinna and successfully survived the implantation, as well as retained human vasculature within the mouse’s circulatory system. By using multiphoton microscopy, the researchers could visualize how the parasite Plasmodium falciparum infected erythrocytes and stimulated vascular cytoadherence in human physiology. Xenograft models provide ample possibilities for further research and testing in more applicable ways for humans (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004987/).
Xenograft models require the use of immunodeficient mice. Usually, nude mice and NOD/SCID standards are most effective for xenograft research studies. In the United States, animal handling and maintenance is regulated by the IACUC and often compliance with GLP standards is required for drug development studies and subsequent IND applications (per FDA requirements). Xenograft study reports must include experimental design, detailed SOPs for all procedures, health reports, and related experimental data. Variety and availability make xenografts particularly applicable to pilot studies, proof of concept studies, and experiments dealing with rare tumor types.
A unique feature of xenograft models is the ability to manipulate the cells prior to implantation. Cells can be engineered to express exogenous regulatory RNAs (RNAi, miRNAs) or recombinant proteins. Custom engineering gives researchers control over tumor characteristics and can reduce confounding effects caused by a heterogenous background.
Commercial Xenografts
Commercial xenografting services are now more prominent, but experience and quality certification is seldom found. Altogen Labs is a leading provider of in vivo xenograft services with over 80 validated xenograft models available. Altogen Labs performs evaluations of the potency of treatments and drugs based off the rate of staged, subcutaneously engrafted tumors in xenograft mouse models. Altogen Labs strives to expand and improve upon xenograft model CRO service continually. Studies utilizing xenograft models are performed in an IACUC-regulated and GLP-compliant barrier facility with associated setups suitable for various compound administration types (IV, IP, IT, oral gavage, inhalation, syringe pump, etc.) as well as a large number of dose regimens to test biologics and assess the efficacy of all types of treatments.
The following assays are commonly utilized for xenograft in vivo studies:
- Tumor growth delay (latency, TGD)
- Tumor growth inhibition (TGI)
- Toxicity
- Survival
- Combination approaches
Altogen Labs in vivo xenograft services can also assist you in efficacy screening and proof-of-concept studies using any of their 80+ validated cancer cell line CDX xenograft models including brain, breast, prostate, colon, peripheral, blood, pancreas, kidney, ovarian, and thyroid cancer. Orthotopic xenograft models are performed to help study the effects of drug substances on human tumors transplanted to the equivalent mouse organ. Orthotropic xenografts are effective for assessing the consequences of drugs on preventing metastasis of the tumor under study.
Metabolic Disease Models
Diabetes, heart disease and even cancer have been linked to metabolism of glucose in the human body. In vivo xenograft services can also be extended to measure glucose metabolism in mice and rats under minimum stress. Xenograft animal models are often conducted for drug safety and validation. Experiments involving such models can elicit mechanisms of action and open doors to further research and development with clinical implications. Studies are performed on different levels; from examining the metabolism in animal models to isolated tissue and tissue culture cell-based assays.
Metabolic research includes assays such as:
- Oral glucose tolerance test
- Insulin tolerance test
- Hormone and cytokine assays
- Signal Transduction
- Determination of parent compound and circulating metabolites.
Inflammation Disease Models
Xenograft animal models are a useful experimental tool in conducting in vivo evaluation of drug substances that modulate inflammatory pathways. Timed and dose-response studies are utilized to get a better understanding of the hematological and biochemical limits that differentiate the main stage of a disease and identify the effects of the candidate drug.
Common inflammation disease models are:
- Carrageenan Paw Edema Model
- Collagen Induced Arthritis Model
- Adjuvant Induced Arthritis Model
- LPS induced inflammatory Model
- Hormone and cytokine assays
- Signal Transduction
- Evidence of parent compound and circulating metabolites.
Validated Cell Line Derived Xenograft (CDX) animal models:
| Tumor Type: | Altogen Labs in-house validated CDX xenograft models: |
| Brain | LN229, SF268, SF295, SF539, SK-N-AS, SNB-19, SNB-75, U-251 MG, U87 MG, U87-Luc |
| Breast Cancer | 4T1, BT474, HS578T, KPL-4, MCF-7, MDA-MB-157, MDA-MB-231, MDA-MB-453, MDA-MB-468, T47D |
| Colon | COLO-205, CT-26, DLD-1, HCT116, HT-29, KM-12, L0Vo, LS-174T, MC38, RKO, SW480, SW-620, WiDr |
| Gastric | AGS, HS746T, MKN-45, NCI-N87, SNU-16, SGC-7901 |
| Hepatocellular / Liver | H22, Hepa1-6, Hep3B, HepG2, SK-HEP-1, SMMC-7721 |
| Leukemia/Lymphoma | A20, DOHH2, EL-4, HL-60, K-562, Karpas-299, MOLM-13, Ramos, Raji |
| Lung | A549, Calu-3, Calu-6, H226, H460, H1155, Huh7, NCI-H226, NCI-H1975 |
| Melanoma | A375, A2058, B16, SK-MEL-2 |
| Other | FaDu, HeLa |
| Ovarian | OV-CAR3, SKOV-3 |
| Pancreas | AsPC-1, BxPc-3, MIAPaCa-2, PANC-1 |
| Prostate | DU-145, LNCaP, PC-3 |
| Renal / Kidney | 786-O, A498, Caki-1, HEK-293, Renca |
| Sarcoma | SJSA-1, S180 |
Validated Metastatic CDX Models:
Validated Metastatic CDX Models: