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

Enrica Balza, Barbara Carnemolla, Lorenzo Mortara, Patrizia Castellani, Debora Soncini, Roberto S. Accolla, Laura Borsi

Research output: Contribution to journalArticlepeer-review

Abstract

L19-IL2 and L19TNFα are fusion proteins composed of L19(scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform and IL-2 or TNFa. Because of the tumor targeting properties of L19, IL-2 and TNFa concentrate at therapeutic doses at the tumor vascular level. To evaluate the therapeutic effects of L19-IL2 and L19mTNFa in neuroblastoma (NB)-bearing mice, A/J mice bearing Neuro2A or NIE115 NB were systemically treated with L19-IL2 and L19mTNFα, 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 L19mTNFα, 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 L19mTNFα 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.

Original languageEnglish
Pages (from-to)101-110
Number of pages10
JournalInternational Journal of Cancer
Volume127
Issue number1
DOIs
Publication statusPublished - Jul 1 2010

Keywords

  • Angiogenesis
  • Immunotherapy
  • Neuroblastoma
  • Oncofetal fibronectin
  • Tumor targeting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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