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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models
Ke Xie1, Rui-Zhen Bai1, Yang Wu1
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang, No 37, Chengdu, Sichuan 610041, PR China.
Background:
Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor.
Methods:
The protective effects and therapeutic anti-tumor immunity mediated by the DNA vaccine were investigated in mouse models. Anti-angiogenesis effects were detected by immunohistochemical staining and the alginate-encapsulate tumor cell assay. The mechanism of action of the DNA vaccine was primarily explored by detection of auto-antibodies and CTL activity.
Results:
The DNA vaccine elicited a strong, protective and therapeutic anti-tumor immunity through an anti-angiogenesis mechanism in mouse models, mediated by the stimulation of an antigen-specific response against mFlk-1.
Conclusion:
Our study shows that a DNA vaccine based on a xenogeneic homologue plasmid DNA induced autoimmunity against VEGFR-2, resulting in inhibition of tumor growth. Such vaccines may be clinically relevant for cancer immunotherapy.
Insights
This study developed a DNA vaccine using a xenogeneic VEGFR-2 homologue to target tumor angiogenesis. The vaccine successfully induced anti-tumor immunity and inhibited tumor growth, showing potential for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2, are crucial for tumor angiogenesis.
- Inhibiting the VEGF-VEGFR-2 pathway offers a potential strategy for cancer treatment.
- Human VEGFR-2 was utilized as a model antigen to assess xenogeneic DNA vaccine feasibility.
Purpose of the Study:
- To explore the efficacy of a plasmid DNA vaccine based on a xenogeneic VEGFR-2 homologue for cancer immunotherapy.
- To investigate the potential of inducing anti-tumor immunity and inhibiting tumor growth via this novel vaccine approach.
Main Methods:
- Mouse models were used to evaluate the DNA vaccine's protective and therapeutic anti-tumor immunity.
- Anti-angiogenesis effects were assessed using immunohistochemical staining and an alginate-encapsulate tumor cell assay.
- Mechanisms of action were explored through auto-antibody detection and cytotoxic T-lymphocyte (CTL) activity assays.
Main Results:
- The DNA vaccine demonstrated potent protective and therapeutic anti-tumor immunity in mouse models.
- A significant anti-angiogenesis effect was observed, mediated by an antigen-specific response against mouse VEGFR-2 (mFlk-1).
Conclusions:
- A DNA vaccine utilizing a xenogeneic homologue induced autoimmunity against VEGFR-2, leading to tumor growth inhibition.
- This approach holds clinical relevance for developing novel cancer immunotherapies.

