Innovative DNA vaccine to break immune tolerance against tumor self-antigen

Tae Heung Kang, Chih Ping Mao, Victor La, Alexander Chen, Chien-Fu Hung, Tzyy Choou Wu

Research output: Contribution to journalArticle

Abstract

Vaccination is, in theory, a safe and effective approach for controlling disseminated or metastatic cancer due to the specificity of the mammalian immune system, yet its success in the clinic has been hampered thus far by the problem of immune tolerance to tumor self-antigen. Here we describe a DNA vaccination strategy that is able to control cancer by overcoming immune tolerance to tumor self-antigen. We engineered a DNA construct encoding a dimeric form of a secreted single-chain trimer of major histocompatibility complex class I heavy chain, β2-microglobulin, and peptide antigen linked to immunoglobulin G (SCT-Ag/IgG). The chimeric protein was able to bind to antigen-specific CD8 + T cells with nearly 100% efficiency and strongly induce their activation and proliferation. In addition, the chimeric protein was able to coat professional antigen-presenting cells through the Fc receptor to activate antigen-specific CD8+ T cells. Furthermore, intradermal vaccination with DNA-encoding SCT-Ag/IgG could generate significant numbers of cytotoxic effector T cells against tumor self-antigen and leads to successful therapeutic outcomes in a preclinical model of metastatic melanoma. Our data suggest that the DNA vaccine strategy described in the current study is able to break immune tolerance against endogenous antigen from melanoma and result in potent therapeutic antitumor effects. Such strategy may be used in other antigenic systems for the control of infections and/or cancers.

Original languageEnglish (US)
Pages (from-to)181-188
Number of pages8
JournalHuman Gene Therapy
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2013

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Immune Tolerance
DNA Vaccines
Autoantigens
Neoplasm Antigens
CD8 Antigens
Vaccination
Immunoglobulin G
T-Lymphocytes
DNA
Melanoma-Specific Antigens
Neoplasms
Fc Receptors
Therapeutic Uses
Antigen-Presenting Cells
Infection Control
Major Histocompatibility Complex
Immune System
Melanoma
Proteins
Antigens

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Innovative DNA vaccine to break immune tolerance against tumor self-antigen. / Kang, Tae Heung; Mao, Chih Ping; La, Victor; Chen, Alexander; Hung, Chien-Fu; Wu, Tzyy Choou.

In: Human Gene Therapy, Vol. 24, No. 2, 01.02.2013, p. 181-188.

Research output: Contribution to journalArticle

Kang, Tae Heung ; Mao, Chih Ping ; La, Victor ; Chen, Alexander ; Hung, Chien-Fu ; Wu, Tzyy Choou. / Innovative DNA vaccine to break immune tolerance against tumor self-antigen. In: Human Gene Therapy. 2013 ; Vol. 24, No. 2. pp. 181-188.
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