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

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

Author information

1
Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. Electronic address: Nicolle.rekers@maastrichtuniversity.nl.
2
Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
3
Department of Internal Medicine, Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
4
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, The Netherlands.
5
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Switzerland.

Abstract

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

PMID:
26138057
DOI:
10.1016/j.radonc.2015.06.019
[Indexed for MEDLINE]
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