DNA and adenoviral vectors encoding carcinoembryonic antigen fused to immunoenhancing sequences augment antigen-specific immune response and confer tumor protection

Hum Gene Ther. 2006 Jan;17(1):81-92. doi: 10.1089/hum.2006.17.81.


A panel of vectors was constructed to encode carcinoembryonic antigen (CEA) fused at its C-terminal end to various polypeptides, so as to compare their immunogenicity by plasmid DNA immunization and adenovirus injection in wild-type and CEA transgenic (CEA.tg) mice. Fusions between CEA and the minimized domain of tetanus toxin fragment C (CEA-DOM) or the Fc portion of IgG1 (CEA-FcIgG) were identified as highly immunogenic and elicited significant CEA-specific antibody and CD8+ T cell responses. CEA.tg mice were protected from tumor growth on challenge with MC38-CEA tumor cells only when immunized with repeated injections of plasmid pV1J/CEA-DOM followed by Ad/CEA-DOM. Depletion of T-regulatory cells resulted in an increased immune response and antitumor effect with DNA plus adenovirus immunization. In addition, this protective effect was abrogated if the NK, CD4+, or CD8+ cell population from immunized mice was depleted before tumor challenge. Passive transfer studies demonstrated that CD4+ and CD8+ T cells and antibodies contributed to the antitumor effect, thus suggesting that a genetic vaccine based on the use of plasmid DNA and adenoviral vectors encoding CEA fused to immunoenhancing sequences augments CEA-specific immune responses and effectively protects from tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Blood Proteins / genetics*
  • Blood Proteins / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • Carcinoembryonic Antigen / biosynthesis
  • Carcinoembryonic Antigen / genetics*
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / therapeutic use
  • Cytokines / drug effects
  • Epitopes / immunology
  • Genetic Vectors*
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms / immunology*
  • Neoplasms / prevention & control
  • Plasmids / genetics
  • Receptors, Interleukin-2 / drug effects
  • Recombinant Fusion Proteins
  • Tetanus Toxoid / immunology
  • Transfection


  • Blood Proteins
  • Carcinoembryonic Antigen
  • Cytokines
  • Epitopes
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Tetanus Toxoid
  • immunoenhancing factor