DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice

Jun Cao1, Yiqi Jin, Wei Li

  • 1Interventional Oncology, Dahua Hospital, Xuhui District, Shanghai 200237, China.

BMC Immunology
|August 15, 2013
PubMed
Abstract

Insights

Targeting dendritic cells (DC) with DNA vaccines enhances anti-tumor immunity. Combining DC-targeted DNA vaccines with regulatory T cell (Treg) depletion effectively treats established breast cancer in mice.

Area of Science:

  • Immunology
  • Oncology
  • Vaccine Development

Background:

  • DNA vaccines show promise for cancer immunotherapy but often fail to induce durable anti-tumor immunity.
  • Dendritic cells (DCs) are crucial for antigen processing and presentation in initiating immune responses.
  • Targeting DCs can potentially enhance the efficacy of cancer vaccines.

Purpose of the Study:

  • To develop and evaluate a DC-targeted DNA vaccine for HER2/neu-positive breast cancer.
  • To investigate the anti-tumor efficacy and underlying mechanisms of this targeted vaccine in mouse models.
  • To assess the combination therapy of DC-targeted DNA vaccine with regulatory T cell (Treg) depletion.

Main Methods:

  • Constructed a DC-targeting DNA vaccine by fusing HER2/neu antigen to a single-chain antibody fragment (scFvNLDC-145) targeting DEC-205 on DCs.
  • Administered the vaccine in mouse breast cancer models (D2F2/E2 and BALB-neuT).
  • Evaluated immune responses (cellular and humoral), tumor protection, and tumor regression, with and without Treg depletion using cyclophosphamide.

Main Results:

  • The scFvNLDC-145 targeted DNA vaccine successfully delivered antigens to DCs in vivo.
  • Vaccination significantly enhanced HER2/neu-specific cellular and humoral immune responses, inducing long-lasting immune memory.
  • The targeted vaccine provided protection against HER2/neu-positive tumors and, when combined with Treg depletion, induced regression of established tumors and retarded spontaneous tumor development.

Conclusions:

  • DC-targeted DNA vaccines can induce potent antigen-specific immune responses.
  • Combining DC-targeted DNA vaccines with Treg depletion offers significant therapeutic anti-tumor activity.
  • This approach provides a strong rationale for developing targeted DNA vaccines for cancer treatment.

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