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A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8+T lymphocytes in a murine melanoma model.

ABSTRACT: The p42.3 gene was recently identified and characterized as having tumor-specific and mitosis phase-dependent expression in many types of cancer. This suggested that p42.3 antigen could be used as a target for vaccines against cancers. In this study, we immunized C57BL/6 mice with a DNA vaccine encoding p42.3. We used intramuscular injection with electroporation, either before or after challenge with tumor B16F10 cells. Vaccination with pcDNA3-p42.3 induced some degree of antitumor effect both therapeutically and prophylactically, as evaluated by the inhibition of tumor growth and decrease in tumor weight. Immunized mice showed a high level of specific cytotoxic activity against the p42.3 protein in vivo and had activated CD8 T cells that secreted IFN-?, perforin, and granzyme B in response to stimulation with the antigen in vitro. Thus, this study presents the DNA vaccination against novel tumor target p42.3 as a promising antitumor modality.

SUBMITTER: Liu H

PROVIDER: S-EPMC3906404 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8+T lymphocytes in a murine melanoma model.

Liu Hu H Geng Shuang S Feng Congcong C Xie Xiaoping X Wu Bing B Chen Xuan X Zou Qiang Q Wang Shuang S Cui Jiantao J Xing Rui R Li Wenmei W Lu Youyong Y Wang Bin B

Human vaccines & immunotherapeutics 20130604 10

The p42.3 gene was recently identified and characterized as having tumor-specific and mitosis phase-dependent expression in many types of cancer. This suggested that p42.3 antigen could be used as a target for vaccines against cancers. In this study, we immunized C57BL/6 mice with a DNA vaccine encoding p42.3. We used intramuscular injection with electroporation, either before or after challenge with tumor B16F10 cells. Vaccination with pcDNA3-p42.3 induced some degree of antitumor effect both t ...[more]

PMID: 24051432

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Project description:Rationale: The development of a highly effective and tumor-specific therapeutic strategy, which can act against the primary tumor and also condition the host immune system to eliminate distant tumors, remains a clinical challenge. Methods: Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP@mSiO2@DOX-ZnO) that integrates photothermal properties of gold nanoparticles (NPs), pH-responsive properties and preferential selectivity to tumor cells of ZnO QDs and chemotherapeutic agent into a single NP. The photothermal performance, pH-triggered release and preferential phagocytic ability were assessed. The induced anti-tumor immunity was determined by analyzing immune cell profile in tumor in vivo and molecular mechanism were identified by detecting expression of immunogenic cell death (ICD) markers in vitro. Moreover, mice models of unilateral and bilateral subcutaneous melanoma and lung metastasis were established to evaluate the antitumor effects. Results: As an efficient drug carrier, ZnO-capped NPs guarantee a high DOX payload and an in vitro, efficient release of at pH 5.0. In murine melanoma models, the nanocomposite can significantly inhibit tumor growth for a short period upon low-power laser irradiation. Importantly, ZnO NPs not only demonstrate preferential selectivity for melanoma cells but can also induce ICD. Meanwhile, AuNP@mSiO2-based photothermal therapy (PTT) and DOX are directly cytotoxic towards cancer cells and demonstrate an elevated ICD effect. The induced ICD promotes maturation of dendritic cells, further stimulating the infiltration of effector T cells into tumor sites, preventing tumor growth and distant lung metastases. Conclusions: This study highlights the novel mechanism of ZnO-triggered anti-tumor immunity via inducing ICD. Additionally, we shed light on the multifunctionality of nanocomposites in delivering localized skin tumor therapy as well as inhibiting metastatic growth, which holds great promise in clinical applications.

Dataset Information

A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8+T lymphocytes in a murine melanoma model.

Publications

A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8+T lymphocytes in a murine melanoma model.

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