Klin Padiatr 2013; 225 - A38
DOI: 10.1055/s-0033-1343655

Development of dual function MYCN-DNA vaccines for anti-neuroblastoma immunotherapy

D Reker 1, A Stermann 1, N Huebener 2, N Siebert 1, HN Lode 1
  • 1University Medicine Greifswald Pediatric Hematology/Oncology, Greifswald
  • 2Max-Delbrück-Center for molecular medicine Berlin-Buch, Berlin; Germany

Introduction: We recently showed that MYCN-DNA minigene vaccination is an effective immunotherapeutic approach to treat MYCN-amplified neuroblastoma (NB) in vivo. To further enhance the therapeutic efficacy, we designed dual function DNA-vaccines driving the expression of MYCN antigens and interleukins (ILs) such as IL-2, IL-15 and IL-21 in one vector.

Methods/Results: For this purpose, previously established MYCN minigenes were ligated into the bicistronic vector pIRES in combination with the cDNA encoding for IL-2, IL-15 or IL-21.

IL expression was verified in vitro by transient transfection of CHO cells and subsequent ELISA and Western blot. Functionality ILs was confirmed in T cell proliferation assays and by analysis of MHC expression on dendritic cells following incubation with supernatant from transfected CHO cells by flow cytometry.

Effects of these DNA vaccines delivered by attenuated Salmonella typhimurium on anti-tumor immune response in vivo using a syngeneic MYCN-over expressing NB mouse model will be reported at the meeting.

Conclusion: In summary, we designed dual function MYCN-DNA vaccines and report functional activity for adjuvant DNA vaccination approaches against MYCN-over expressing neuroblastoma.