IMMUNOTHERAPY, INTERLEUKIN-2, RADIOTHERAPY, TREATMENT RESISTANCE
Immunotherapy represents a highly promising treatment strategy for cancer. Recent studies revealed that loco-regional irradiation of the primary tumor leads to the release of danger signals, cytokines and chemokines recruiting immune cells to the tumor site. This results in immune-mediated anti-tumor effects, which could potentially reduce tumor dissemination and might even lead to an immune-mediated control of un-irradiated tumor nodules. We have recently developed and characterized a novel anti-human IL-2 (hIL-2) antibody, termed NARA1. NARA1 in complex with hIL-2 allows the preferential stimulation of CD8+ T and NK cells, whereas IL-2-mediated stimulation of immunosuppressive Treg cells is disfavored by such hIL-2/NARA1 complexes. This results in potent anti-tumor responses with reduced adverse effects and lower intratumoral levels of Treg cells. We here investigate the combined treatment modality of radiotherapy with hIL-2/NARA1 complexes in pre-clinical lung and melanoma tumor models. Initial experiments will be performed to identify an optimal treatment regimen for this combined treatment modality, followed by efficacy- and mechanistic-oriented experiments in orthotopic tumor models. These studies on the combined treatment modality of radiotherapy with hIL-2/NARA1 complexes represent a novel treatment approach in the field of radioimmunotherapy to overcome treatment-induced resistance.