Combination of radiotherapy with the immunocytokine L19-IL2: Additive effect in a NK cell dependent tumour model

Radiother Oncol. 2015 Sep;116(3):438-42. doi: 10.1016/j.radonc.2015.06.019. Epub 2015 Jun 29.


Background and purpose: Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses.

Material and methods: In syngeneic F9 tumour bearing 129/FvHsd mice tumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry.

Results: Tumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression.

Conclusion: An additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression.

Keywords: Cancer; ED-B; F9; Immunotherapy; MHCI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Drug Administration Schedule
  • Fibronectins / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Immunity, Cellular / immunology
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred Strains
  • Neoplasms / immunology
  • Neoplasms / radiotherapy*
  • Radioimmunotherapy / methods*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacology*


  • Antineoplastic Agents
  • FN1 protein, human
  • Fibronectins
  • Histocompatibility Antigens Class I
  • L19-IL2 immunocytokine
  • Recombinant Fusion Proteins