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Updated: Mar 27, 2026

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
DC targeting DNA vaccines induce protective and therapeutic antitumor immunity in mice
Qun Wang1, Wei Cao1, Zhi-Gang Yang1
1Department of Surgical Oncology, Shanghai Shidong Hospital Shanghai, China.
Background:
Anti-CD11c antibodies target to the CD11c receptor that mediates antigen presentation to T cells by dendritic cells (DCs). To exploit these properties for immunization purposes, we obtained DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from N418 (scFv(N418)), a monoclonal antibody binding the mouse DC-restricted surface molecule CD11c, and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models.
Methods:
Induction of humoral and cellular immune responses and antitumoral activity of the DNA vaccines were tested in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB-neuT mice developing spontaneous Neu-driven mammary carcinomas.
Results:
Upon injection of the breast tumor cell line D2F2/E2 (stably expressing human wild-type HER2), scFv(N418)-HER2 immunized mice were protected against tumor growth. Even more important for clinical applications, we were able to substantially slow the growth of implanted D2F2/E2 cells by injection of scFv(N418)-HER2 conjugates into tumor bearing hosts. The existing tumors were eradicated by treatment with scFv(N418)-HER2 combined with low-dose cyclophosphamide (CTX), which can make a temporary regulatory T cells (Treg) depletion. What's more, in combination with the low-dose CTX, vaccination with scFv(N418)-neu significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice.
Conclusion:
Our results show that DNA vaccine which targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity.
Insights
This study developed a novel DNA vaccine targeting dendritic cells (DCs) to combat breast cancer. The scFv(N418)-HER2 conjugate showed significant antitumoral efficacy in mouse models, offering a promising strategy for long-lasting antitumor immunity.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Anti-CD11c antibodies target CD11c receptors on dendritic cells (DCs) for antigen presentation.
- Developing DC-targeting DNA vaccines can enhance immunization strategies.
- Tumor-associated antigen HER2/neu ectodomain was fused with scFv(N418) for DC targeting.
Purpose of the Study:
- To explore the antitumoral efficacy of DC-targeting DNA vaccines.
- To investigate the underlying mechanisms of these vaccines in mouse breast cancer models.
- To evaluate the potential for inducing long-lasting antitumor immunity.
Main Methods:
- Constructed scFv(N418)-HER2 DNA vaccines.
- Tested vaccine efficacy in transplantable HER2/neu-expressing murine tumor models.
- Assessed humoral and cellular immune responses and antitumoral activity.
Main Results:
- scFv(N418)-HER2 immunization protected against tumor growth in mice.
- Conjugate injection slowed tumor growth in existing tumors.
- Combination therapy with low-dose cyclophosphamide eradicated tumors and retarded spontaneous mammary carcinomas.
Conclusions:
- DC-targeting DNA vaccines via antibody-antigen conjugates offer a novel approach.
- This strategy can induce long-lasting antitumor immunity.
- Potential clinical applications for breast cancer treatment.
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