Survivin minigene DNA vaccination is effective against neuroblastoma

Int J Cancer. 2009 Jul 1;125(1):104-14. doi: 10.1002/ijc.24291.


The inhibitor of apoptosis protein survivin is highly expressed in neuroblastoma (NB) and survivin-specific T cells were identified in Stage 4 patients. Therefore, we generated a novel survivin minigene DNA vaccine (pUS-high) encoding exclusively for survivin-derived peptides with superior MHC class I (H2-K(k)) binding affinities and tested its efficacy to suppress tumor growth and metastases in a syngeneic NB mouse model. Vaccination was performed by oral gavage of attenuated Salmonella typhimurium SL7207 carrying pUS-high. Mice receiving the pUS-high in the prophylactic setting presented a 48-52% reduction in s.c. tumor volume, weight and liver metastasis level in contrast to empty vector controls. This response was as effective as a survivin full-length vaccine and was associated with an increased target cell lysis, increased presence of CD8(+) T-cells at the primary tumor site and enhanced production of proinflammatory cytokines by systemic CD8(+) T cells. Furthermore, depletion of CD8(+) but not CD4(+) T-cells completely abrogated the pUS-high mediated primary tumor growth suppression, demonstrating a CD8(+) T-cell mediated effect. Therapeutic vaccination with pUS-high led to complete NB eradication in over 50% of immunized mice and surviving mice showed an over 80% reduction in primary tumor growth upon rechallenge in contrast to controls. In summary, survivin-based DNA vaccination is effective against NB and the rational minigene design provides a promising approach to circumvent potentially hazardous effects of using full length antiapoptotic genes as DNA vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Drug Design
  • Female
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Immunoenzyme Techniques
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Inbred A
  • Microtubule-Associated Proteins / genetics*
  • Neuroblastoma / immunology
  • Neuroblastoma / prevention & control*
  • Peptide Fragments / therapeutic use
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Vaccination
  • Vaccines, DNA / immunology*


  • Birc5 protein, mouse
  • Cytokines
  • Histocompatibility Antigens Class I
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Peptide Fragments
  • RNA, Messenger
  • Repressor Proteins
  • Survivin
  • Vaccines, DNA