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Updated: May 28, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model
T Nguyen-Hoai1, G Baldenhofer, M S Sayed Ahmed
1Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Berlin-Buch and Campus Virchow-Klinikum, Berlin, Germany.
Abstract:
Secondary lymphoid-tissue chemokine (SLC/CCL21) is a CC chemokine that is constitutively expressed in various lymphoid tissues and binds to chemokine receptor CCR7 on mature dendritic cells (DCs) and distinct T-and B-cell sub-populations. In vivo, CCL21 regulates the encounters between DC and T cells and thus is a key regulator of adaptive immune responses. We asked whether CCL21 is able to augment immunogenicity of a DNA-based vaccine against Her2/neu in a Balb/c mouse model with syngeneic Her2/neu+ tumor cells (D2F2/E2). Mice were vaccinated intramuscularly with plasmid DNA (pDNA) on day 1 and boosted on day 15; tumor challenge was performed subcutaneously on day 25. Coexpression of CCL21 and Her-2/neu resulted in induction of a TH1-polarized immune response and substantial improvement of the protective effect of the DNA vaccine. Coexpression of tumor antigen pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) as adjuvants led to further improvement of protection by the vaccine (70% tumor-free mice on day 35 vs 40% with either adjuvant alone vs 5-10% with tumor antigen alone). Our results show that CCL21 is a potent adjuvant for DNA vaccination, particularly in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu/CCL21/GM-CSF) vaccine might be particularly promising in minimal residual Her2/neu+ breast cancer.
Insights
Secondary lymphoid-tissue chemokine (CCL21) enhances DNA vaccine immunity against Her2/neu tumors. Combining CCL21 with granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly improves protective effects, showing promise for breast cancer treatment.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Secondary lymphoid-tissue chemokine (CCL21) is crucial for adaptive immunity by regulating T-cell and dendritic cell interactions.
- CCL21 binds to chemokine receptor CCR7 on mature dendritic cells and specific T- and B-cell subsets.
- CCL21 plays a key role in vivo for initiating adaptive immune responses.
Purpose of the Study:
- To investigate if CCL21 can enhance the immunogenicity of a DNA vaccine targeting Her2/neu.
- To evaluate the efficacy of CCL21 as a standalone adjuvant and in combination with GM-CSF.
Main Methods:
- A DNA vaccine encoding Her2/neu was administered to Balb/c mice.
- Mice were vaccinated intramuscularly with plasmid DNA (pDNA) encoding Her2/neu, CCL21, and/or GM-CSF.
- Tumor challenge with syngeneic Her2/neu+ tumor cells (D2F2/E2) was performed to assess vaccine efficacy.
Main Results:
- Coexpression of CCL21 with Her2/neu in the DNA vaccine induced a TH1-polarized immune response.
- CCL21 significantly improved the protective effect of the DNA vaccine against Her2/neu tumors.
- Combining pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) resulted in 70% tumor-free mice, a marked improvement over single adjuvants or tumor antigen alone.
Conclusions:
- CCL21 acts as a potent adjuvant for DNA vaccination.
- The combination of CCL21 and GM-CSF offers superior protection, suggesting a promising therapeutic strategy.
- This combined vaccine approach may be particularly beneficial for treating minimal residual Her2/neu+ breast cancer.
