Therapeutic HER2/Neu DNA vaccine inhibits mouse tumor naturally overexpressing endogenous neu

Chi Chen Lin, Ching Wen Chou, Ai Li Shiau, Cheng Fen Tu, Tai-Ming Ko, Yi Ling Chen, Bei Chang Yang, Mi Hua Tao, Ming Derg Lai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The therapeutic efficacy of HER2/c-erbB-2/neu DNA immunization on mouse tumor cells expressing exogenous human or rat p185neu but not on mouse tumor cells naturally expressing mouse p185neu has been demonstrated. We investigated the feasibility of using N-terminal rat neu DNA immunization on mouse tumor overexpressing endogenous p185neu and enhancing the therapeutic efficacy of this vaccine by fusion to various cytokine genes, including interleukin-2 (IL-2), interleukin-4 (IL-4), or granulocyte-macrophage colony-stimulating factor. In a therapeutic model, N′-neu-IL-2 DNA vaccine was significantly better than N′-neu DNA vaccine, and N′-neu DNA vaccine was significantly better than control DNA or N′-neu-IL-4 DNA vaccine. The therapeutic efficacy of DNA vaccines was correlated with tumor infiltration of CD8+ T cells. Depletion of CD8+ T cells completely abolished the therapeutic effects of N′-neu-IL-2 DNA vaccine and N′-neu DNA vaccine. Depletion of CD4+ T cells after tumor implantation had no influence on N′-neu-IL-2 DNA vaccine, but enhanced the therapeutic efficacy of N′-neu DNA vaccine. Our results demonstrate that rat N′-neu DNA vaccine has a therapeutic effect on established tumor through the CD8+ T-cell-dependent pathway. Depletion of CD4+ T cells or fusion to the IL-2 gene can thus further enhance the therapeutic effects of N′-neu DNA immunization on mouse tumor expressing endogenous p185neu.

Original languageEnglish
Pages (from-to)290-301
Number of pages12
JournalMolecular Therapy
Volume10
Issue number2
DOIs
StatePublished - 1 Aug 2004

Keywords

  • CD4
  • CD8
  • DNA vaccine
  • GM-CSF
  • IL-2
  • IL-4
  • MBT-2
  • Neu

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