Therapy-induced antitumor vaccination in neuroblastomas by the combined targeting of IL-2 and TNFalpha

Int J Cancer. 2010 Jul 1;127(1):101-10. doi: 10.1002/ijc.25018.


L19-IL2 and L19TNFalpha are fusion proteins composed of L19(scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform and IL-2 or TNFalpha. Because of the tumor targeting properties of L19, IL-2 and TNFalpha concentrate at therapeutic doses at the tumor vascular level. To evaluate the therapeutic effects of L19-IL2 and L19mTNFalpha in neuroblastoma (NB)-bearing mice, A/J mice bearing Neuro2A or NIE115 NB were systemically treated with L19-IL2 and L19mTNFalpha, alone or in combination protocols. Seventy percent of Neuro2A- and 30% of NIE115-bearing mice were cured by the combined treatment with L19-IL2 and L19mTNFalpha, and further rejected a homologous tumor challenge, indicating specific antitumor immune memory. The immunological bases of tumor cure and rejection were studied. A highly efficient priming of CD4(+) T helper cells and CD8(+) CTL effectors was generated, paralleled by massive infiltration in the tumor tissue of CD4(+) and CD8(+) T cells at day 16 after tumor cell implantation, when, after therapy, tumor volume was drastically reduced and tumor necrosis reached about 80%. The curative treatment resulted in a long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2 type of response. Concluding, L19-IL2 and L19mTNFalpha efficiently cooperate in determining a high percentage of NB cure that, in our experimental models, is strongly associated to the generation of adaptive immunity involving CD4(+) and CD8(+) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Interleukin-2 / administration & dosage*
  • Mice
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy*
  • Tumor Necrosis Factor-alpha / administration & dosage*


  • Cancer Vaccines
  • Interleukin-2
  • Tumor Necrosis Factor-alpha