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Updated: Jul 9, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Chemo-Immunotherapy, a Combination Approach for the Treatment of HER2-Positive Breast Cancer in a Mouse Model
Cenk Serhan Özverel1, Kubilay Doğan Kılıç2, Yiğit Uyanikgil2
1Department of Biology, Faculty of Science, Ege University, Izmir, Türkiye.
Abstract:
The discovery of tumor-associated antigens has been a significant milestone for cancer therapy as the current conventional therapies (radiotherapy, chemotherapy) were found to be insufficient in terms of cancer treatment. Human epidermal growth factor receptor (HER2) is a tumor-associated antigen, aberrantly found in various cancers, including breast cancer. Today, most treatment strategies are skewed toward combination therapies rather than monotherapies, as they have been found primarily ineffective due to patients' resistance mechanisms. A combination of multiple therapeutic approaches (passive/active immunotherapy, conventional therapies) was found to be more effective in the clinic. This study investigated various vaccine combinations against the 4 T1-HER2 xenograft model of Balb/c mice. Eight different groups of vaccine formulations were tested to find the best synergistic combination, including combinations of BM-DC-based vaccine, peptide-based vaccine, anti-PD-L1, Doxorubicin, and QS-21 adjuvant. Triple combination groups of immunotherapies exerted better activities in terms of tumor dimensions as Doxorubicin+BM-DC-HER2/Neu + QS-21 + anti-PD-L1 and Doxorubicin+HER2/Neu + QS-21 + anti-PD-L1 groups significantly decreased tumor dimensions. Similar groups also demonstrated a better stimulation of lymphocytes and IFN-γ cytokine in the flow cytometry study, inducing a HER2/Neu-specific antibody response in ELISA studies. Doxorubicin+BM-DC-HER2/Neu + QS-21 + anti-PD-L1 combination demonstrated significantly higher specific cytotoxicity in lactate dehydrogenase data, as well as the CD4+ and CD8+ responses in the immunohistochemical study. In conclusion, these data indicated that the Doxorubicin+BM-DC + HER2/Neu + QS-21 + anti-PD-L1 vaccine combination synergistically generated a promising activity in terms of tumor dimension and immune response stimulation against the HER2 overexpressing breast cancer model in mice.
Insights
This study explored novel vaccine combinations for HER2-positive breast cancer, finding that a triple therapy including Doxorubicin, BM-DC, HER2/Neu, QS-21, and anti-PD-L1 significantly reduced tumor size and boosted immune responses in mice.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Vaccines
Background:
- Conventional cancer therapies like chemotherapy and radiotherapy show limitations due to patient resistance mechanisms.
- Tumor-associated antigens, such as Human Epidermal Growth Factor Receptor 2 (HER2), are crucial targets for novel cancer treatments.
- Combination therapies are increasingly favored over monotherapies for improved clinical efficacy in cancer treatment.
Purpose of the Study:
- To investigate the synergistic efficacy of various vaccine combinations against a 4T1-HER2 xenograft model in mice.
- To identify the optimal combination therapy for enhancing anti-tumor activity and immune response against HER2-overexpressing breast cancer.
Main Methods:
- Testing eight different vaccine formulations, including combinations of BM-DC-based vaccines, peptide-based vaccines, anti-PD-L1, Doxorubicin, and QS-21 adjuvant.
- Evaluating tumor dimensions, lymphocyte and IFN-γ cytokine stimulation via flow cytometry, HER2/Neu-specific antibody response using ELISA, and specific cytotoxicity via lactate dehydrogenase assay.
- Assessing CD4+ and CD8+ T-cell responses through immunohistochemical analysis.
Main Results:
- Triple combination therapies, particularly Doxorubicin+BM-DC-HER2/Neu+QS-21+anti-PD-L1 and Doxorubicin+HER2/Neu+QS-21+anti-PD-L1, significantly reduced tumor dimensions.
- These combinations also enhanced lymphocyte and IFN-γ cytokine levels, indicating a robust immune stimulation.
- The Doxorubicin+BM-DC+HER2/Neu+QS-21+anti-PD-L1 combination showed superior specific cytotoxicity and significant CD4+/CD8+ T-cell responses.
Conclusions:
- The combination of Doxorubicin, BM-DC, HER2/Neu, QS-21, and anti-PD-L1 demonstrated synergistic anti-tumor activity in a HER2-overexpressing breast cancer mouse model.
- This multi-component vaccine strategy effectively stimulated immune responses, including specific antibody production and cytotoxic T-cell activity.
- The findings suggest this combination therapy holds promise for treating HER2-positive breast cancers.
