Testing Immunotherapies in Syngeneic Models
Cancer immunotherapies are designed to work in conjunction with a patient's immune system to increase native anti-tumor responses. In this field of study, conventional xenograft models lack relevance due to the animals’ immunocompromised status. A syngeneic mouse model (e.g., 4T1 and MC38 cell lines), however, provides an effective approach for studying how cancer therapies perform in the presence of a functional immune system.
Syngeneic Mouse Models
Figure 1: Diagram of syngeneic mouse models. Tumor tissue of the same (murine) genetic background is implanted into a mouse with an intact native immune system.
Syngeneic Mouse Models
Charles River offers a broad range of syngeneic mouse models with well-characterized responses to known immune checkpoint inhibitors (e.g., anti-PDL-1, anti-PD-1, anti-CTLA-4), immune profiling, and genetic evaluation (e.g., whole exome sequencing, RNA-seq). With a portfolio of syngeneic models that are responsive to immunotherapies as well complimentary in vitro and in vivo models in patient-derived xenografts (PDX), humanized models, and target validation, Charles River is your ideal partner to advance your immuno-oncology pipeline.
Syngeneic model selection is often based on:
- Responsiveness to known immune-modulating therapies such as anti-CTLA-4 and anti-PD-1
- Extent and composition of tumor-infiltrating leukocytes (TIL)
We offer syngeneic mouse models with and without profile. Our syngeneic models with profile have been evaluated for response with checkpoint inhibitors and/or chemotherapies. We also offer syngeneic models with growth curves, but no standard agent/checkpoint inhibitor data.
Syngeneic Models With Profile
Histotype Cell Line Bladder MBT-2 Brain GL261 Breast 4T1, EMT-6, E0771 Colon Colon26, CT26, MC38 Leukemia C1498 Lung KLN 205, Lewis Lung, Madison109 Lymphoma A20, E.G7-OVA Melanoma B16F10, CloudmanS91 Pancreatic Pan02 Renal Renca
Syngeneic Models Without Profile*
Histotype Cell Line Breast EMT-6-BRCA1(−/−), EMT-6-BRCA1(+/−), 4T1-BRCA1(+/−) Hepatoma Yoshida Leukemia L1210, P388 Lung KLN205 Lymphoma EL4 Mastocytoma P815 Melanoma YUMM1.7 Neuroblastoma N1E-115 Plasmacytoma J558 Sarcoma EHS
* Note: Although these models have not yet been profiled for response to current standards of care, tumor growth curve data is available.
In addition pharmacological effects and pharmacokinetics of test compounds can be determined in the tumor microenvironment with high sensitivity and temporal resolution by our in vivo microdialysis services. In vivo implantable microdevices can also be used to aid studies by allowing simultaneous in vivo testing of multiple drugs, drug doses, or drug combinations in a single tumor.
Complementary Immunology Assays
As the science evolves, we have worked to enhance our portfolio with additional mouse models of cancer and will continue to expand into additional models that allow for this simulation in vitro and in vivo, including humanized models; genetically altered models; and cytokine response, T-cell activation, and toxicity assays.
Additionally we offer targeted transcriptomics using NanoString gene expression analysis platform to provide information on how therapeutic is regulating the tumor microenvironment.
Have another question or need advice on which model is right for you?
Frequently Asked Questions (FAQs) on Syngeneic Mouse Models
What is a syngeneic mouse model?
Syngeneic mouse models, also known as Allograft mouse tumor systems, consist of tumor tissues derived from the same genetic background as a given mouse strain. As the syngeneic mice retain intact immune systems, they are particularly relevant for studies of immunotherapies. Examples of uses include cancer therapies targeting immune checkpoint or immune co-stimulatory molecules.
What is an orthotopic model?
In orthotopic models, tumors are implanted into the equivalent organ from which the cancer originated. Orthotopic models have a similar tumor microenvironment as the original tumor, which allows for the assessment of tumor development in a model that mimics natural disease progression.
What is a mouse xenograft model?
In mouse xenograft models, human tumor cells are transplanted, either orthotopically or subcutaneously, into immune-compromised mice that will not reject the human cells. Xenograft mouse models allow for the analysis of human tumor response to anti-cancer therapies.
What is flow cytometry?
Flow cytometry is an analytical cell-biology technique that utilizes light to count and profile cells in a heterogenous fluid mixture. Our in-house multiplex flow cytometry enables a comprehensive analysis of the immune system, allowing identification of various cell populations and deep interrogation of an immune response elicited from novel therapeutics.
What oncology models are right for me?
In a complex and changing field, knowing the next step can be difficult. Answer a few brief questions about your research to receive expert guidance on how to advance your oncology program.