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

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.