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

Nicolle H. Rekers*, Catharina M. L. Zegers, Ala Yaromina, Natasja G. Lieuwes, Rianne Biemans, Birgit L. M. G. Senden-Gijsbers, Mario Losen, Evert J. Van Limbergen, Wilfred T. V. Germeraad, Dario Neri, Ludwig Dubois, Philippe Lambin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Web of Science)

Abstract

Background and purpose: Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-1L2 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 (10 Gy) combined with systemic administration of L19-1L2. Immunological responses were investigated using flow cytometry. Results: Tumour growth delay of L19-1L2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-1L2 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 L19-11.2 and therefore this combination could be useful in the absence of tumoural MHCI expression.
Original languageEnglish
Pages (from-to)438-442
JournalRadiotherapy and Oncology
Volume116
Issue number3
DOIs
Publication statusPublished - Sep 2015

Keywords

  • Cancer
  • ED-B
  • Immunotherapy
  • F9
  • MHCI

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