Syngeneic Tumor Model Development
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Syngeneic Tumor Model Development

Syngeneic tumor models are pivotal in cancer research since they provide an unparalleled opportunity to investigate tumor biology and assess the effectiveness of various therapies. At Protheragen, we focus on creating and applying syngeneic tumor models for further development in cancer research and drug development.

Overview of Syngeneic Tumor Models

Syngeneic tumor models are among the most sophisticated and immunologically pertinent techniques in preclinical cancer investigation. These models are created by transplanting tumor cell lines from a specific inbred mouse strain into immunocompetent mice of the same strain. The immune system preservation in syngeneic models is different from what is found in xenografts and patient-derived xenografts (PDXs), which allows for the investigation of immune responses to tumors and therapeutics. Because of the accurate immune representation provided in these models, they are used to study immunotherapies, interactions between tumors and their hosts, and even combinational therapeutic approaches within a controlled and replicable setting.

Some syngeneic tumors present a mesenchymal-like phenotype.Fig.1 Mesenchymal-like phenotype of some syngeneic tumors. (Zhong W., et al., 2020)

Applications of Syngeneic Tumor Models in Cancer Therapeutics Development

  • Drug Screening and Efficacy Evaluation
    Syngeneic models have great value in screening new cancer therapeutics due to their high throughput capabilities. For instance, the MC38 colon cancer model has previously been utilized to test immune checkpoint inhibitors, particularly anti-PD-1 antibodies. These models help test the impact of single-agent and multiple-agent therapies in isolation and together, revealing some synergistic insights. The capability to evaluate the efficacy of drugs in a fully functional immune system context makes syngeneic models highly valuable in narrowing down the best therapeutic options.
  • Tumor Microenvironment Studies
    Researchers can explore the tumor microenvironment more closely because the host's immune system is retained in syngeneic models. This encompasses communication between tumor cells and immune cells, as well as the stroma. It is important to understand these relationships to create effective therapeutic strategies that go beyond simply targeting the cancerous cells and also focus on the surrounding microenvironment that aids cancer cell survival and proliferation. For example, immunotherapy syngeneic model studies have highlighted the significant function immune cells perform in either driving or suppressing tumor progression; thus, aiding the design of immune-based therapies.
  • Metastasis and Recurrence
    Syngeneic models are useful in the study of metastasis and cancer recurrence. Understanding how tumors metastasize can be accomplished by examining the mechanisms of transplanted tumors or watching the spread of cancer cells. These findings can then be used to design therapies aimed at treating metastatic diseases. One example is the 4T1 breast cancer model, which is capable of metastasizing to distant organs and is important in understanding the metastatic process and finding appropriate therapeutic interventions.

Our Services

Protheragen provides comprehensive syngeneic tumor model studies in model development, cell line characterization, in vivo testing, and immunophenotyping. For each client, projects are carried out in consultation with them, ensuring that the tumor models are in accordance with the therapeutic targets, tumor histotypes, and immunologic profiles of interest.

Types of Syngeneic Tumor Models

Cell-Derived Allograft Models

The allograft models we develop use the technique of transplanting tumor cell lines into immunocompetent mice of syngeneic origin. Such models are very popular for high-throughput screening of new immunotherapies and anti-tumor therapies. With the provided expertise, we make certain that the models provided for the study of immune interaction with cancer cells are of high quality and reproducibility and therefore can be relied on.

GEM-Derived Allograft Models

Through the modification of oncogenes or tumor suppressor genes to create spontaneous tumor formation, we generate GEM-derived allograft models. The tumors from these GEM mice are subsequently transplanted into immunocompetent mice of the same genetic background. These models are especially beneficial for investigating the processes of tumor initiation, progression, and metastasis along with evaluating the effectiveness of targeted therapies and immunotherapies.

Humanized Immune Checkpoint Models

To address the limitations of traditional syngeneic models, we have developed humanized immune checkpoint models. These models involve replacing mouse genes with their human counterparts to more accurately evaluate human-specific immunotherapies. By expressing human immune checkpoint proteins in the context of a fully functional mouse immune system, these models provide a more precise platform for preclinical drug testing.

B Cell-Deficient Models

If the immune response of mice to therapeutic agents is likely to interfere with drug efficacy studies, we provide B cell-deficient models. Such models are generated by knocking out the Ig heavy chain gene which abolishes the generation of adaptive antibodies. This decreases the risk of anti-drug antibodies (ADAs) forming which otherwise complicate drug efficacy studies.

Optional Disease Models

Disease Name Species Syngeneic Tumor Models
Breast Cancer Mouse EMT-6, EMT-6 Luc, 4T-1, 4T-1-Luc
Colon Cancer Mouse CT26, CT26-Luc, MC38, MC38-Luc
Liver Cancer Mouse H22, H22- Luc, Hepa1-6, Hepa1-6-Luc
B-cell Lymphoma Mouse A20, A20-Luc
Bladder Cancer Mouse MBT2, MBT2-Luc
Kidney Cancer Mouse Renca, Renca-Luc
Mouse Pancreatic Cancer Mouse Pan02, Pan02-Luc
Mouse Melanoma Mouse B16-F10, B16-F10-Luc, B16
Mouse Lung Cancer Mouse LLC
Mouse Brain Cancer Mouse GL261, GL261-Luc

Protheragen's syngeneic tumor model development services empower researchers and biopharmaceutical innovators to bring transformative cancer therapies from bench to bedside with scientific rigor, clinical relevance, and unmatched operational excellence. If you are interested in our services, please feel free to contact us.

Reference

  • Zhong, Wenyan, et al. "Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors." BMC genomics 21.1 (2020): 2.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.