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Radioimmunotherapy to overcome treatment-related resistances

Principal Investigators

Onur Boyman, Department of lmmunology, University Hospital Zurich
Martin Pruschy, Research Unit for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich

Fellow

Carmen Yong, PhD

Keywords

IMMUNOTHERAPY, INTERLEUKIN-2, RADIOTHERAPY, TREATMENT RESISTANCE

Summary

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.