title: Combination of radiotherapy with the immunocytokine L19-IL2: Additive effect in a NK cell dependent tumour model.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Nicolle H
authors.initials: NH
authors.lastname: Rekers
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Natasja G
authors.initials: NG
authors.lastname: Lieuwes
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Rianne
authors.initials: R
authors.lastname: Biemans
authors.affiliation: Department of Internal Medicine, Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Birgit L M G
authors.initials: BL
authors.lastname: Senden-Gijsbers
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, The Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Losen
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Evert J
authors.initials: EJ
authors.lastname: Van Limbergen
authors.affiliation: Department of Internal Medicine, Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Wilfred T V
authors.initials: WT
authors.lastname: Germeraad
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Switzerland.
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Dubois
authors.affiliation: Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005353:Fibronectins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007111:Immunity, Cellular / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C067625:FN1 protein, human; D005353:Fibronectins; D015395:Histocompatibility Antigens Class I; C554817:L19-IL2 immunocytokine; D011993:Recombinant Fusion Proteins
keywords: Cancer; ED-B; F9; Immunotherapy; MHCI