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Updated: Aug 15, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Preclinical Platform Using a Triple-negative Breast Cancer Syngeneic Murine Model to Evaluate Immune Checkpoint
Nar Bahadur Katuwal1,2, Nahee Park1, Kamal Pandey1
1Hematology and Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
Background/Aim:
To evaluate the feasibility of syngeneic mouse models of breast cancer by analyzing the efficacy of immune checkpoint inhibitors (ICIs) and potential predictive biomarkers.
Materials And Methods:
To establish the murine triple-negative breast cancer (TNBC) models, JC, 4T1, EMT6, and E0771 cells were subcutaneously implanted into female syngeneic mice. When the tumor reached 50-100 mm3, each mouse model was divided into a treatment (using a murine PD-1 antibody) and a no-treatment control group. The treatment group was further divided into the responder and non-responder groups. Potential predictive biomarkers were evaluated by analyzing serum cytokines, peripheral blood T cells and tumor infiltrating immune cells.
Results:
The EMT6 model showed the highest tumor response rate (54%, 6/11) of the syngeneic models: 4T1 (45%, 5/11), JC (40%, 4/10), or E0771 (23%, 3/13). Early changes in tumor size at 7 days post-PD-1 inhibitor treatment predicted the final efficacy of the PD-1 inhibitor. Peripheral blood CD8+ and CD4+ T cells with or without Ki67 expression at 7 days post-PD-1 inhibitor treatment were higher in the finally designated responder group than in the non-responder group. At the time of sacrifice, analyses of tumor infiltrating lymphocytes consistently supported these results. We also demonstrated that retro-orbital blood sampling procedures (baseline, 7 days post-treatment, time of sacrifice) were safe for serum cytokine analyses, suggesting that our preclinical platform may be used for biomarker research using serum cytokines.
Conclusion:
Our syngeneic mouse model of TNBC is a feasible preclinical platform to evaluate ICI efficacy combined with other drugs and predictive biomarkers in the screening process of immune-oncology drug development.
Insights
Syngeneic mouse models effectively predict immune checkpoint inhibitor (ICI) efficacy in triple-negative breast cancer (TNBC). Biomarkers like T cell counts and early tumor size changes identify responders, validating these models for drug development.
Area of Science:
- Oncology
- Immunology
- Preclinical Research
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating novel treatment strategies.
- Immune checkpoint inhibitors (ICIs) show promise, but predictive biomarkers are crucial for patient selection.
- Syngeneic mouse models offer a platform to study anti-tumor immunity and drug efficacy.
Purpose of the Study:
- To assess the feasibility of syngeneic mouse models for evaluating ICI efficacy.
- To identify predictive biomarkers for ICI response in TNBC.
- To establish a preclinical platform for immune-oncology drug development.
Main Methods:
- Four TNBC cell lines (JC, 4T1, EMT6, E0771) were implanted in syngeneic mice.
- Mice received either a PD-1 inhibitor or no treatment.
- Responder and non-responder groups were analyzed for serum cytokines, peripheral blood T cells, and tumor-infiltrating immune cells.
Main Results:
- The EMT6 model demonstrated the highest response rate (54%) to PD-1 inhibition.
- Early tumor size changes at 7 days post-treatment predicted final efficacy.
- Increased peripheral blood CD8+ and CD4+ T cells (with or without Ki67) correlated with response.
- Tumor-infiltrating lymphocytes supported peripheral blood findings, and serum cytokine analysis was feasible.
Conclusions:
- Syngeneic TNBC mouse models are feasible for evaluating ICI efficacy and biomarkers.
- These models facilitate the screening of immune-oncology drugs.
- The established platform supports biomarker research using serum cytokines.
