Erb‐(IL10)2 induces abscopal antitumor effects of radiotherapy through the activation and recruitment of lymph node CD8+ T cells

Abstract

Abstract Objective Although radiotherapy (RT) has been widely used in cancer treatment, it provides limited benefits in patients with metastatic cancers due to rare abscopal antitumor effects. Recent progress in cancer immunotherapy provides a potential new strategy to boost the abscopal antitumor effects of RT. Methods We fused interleukin 10 (IL10) dimer onto the anti‐epidermal growth factor receptor antibody cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The antitumor effect and biological activity of Erb‐(IL10)2 were measured in the B16‐EGFR‐OVA tumor model. In vivo cell depletion and flow cytometry analyses were used to assess the mechanism of antitumor effects. Results Erb‐(IL10)2 treatment alone showed modest tumor growth inhibition, while local single dose RT (10 Gy) retarded irradiated tumor growth without affecting the growth of nonirradiated tumors. Notably, the combination therapy of RT and Erb‐(IL10)2 not only additively inhibited irradiated tumor growth but also induced abscopal antitumor responses. In vivo depletion of CD8+ T cells abrogated the combinational antitumor effects, while blocking lymphocyte trafficking through FTY720 treatment abolished the abscopal antitumor responses without affecting the antitumor effects on the irradiated tumor sites. Conclusion This study provides evidence for the radiosensitive role of Erb‐(IL10)2 in the B16‐EGFR‐OVA tumor model. Our findings suggest a novel strategy to elicit the abscopal antitumor effects of RT by combining tumor‐targeted therapy with IL10.

Keywords

• abscopal effect
• radiotherapy
• tumor‐targeted IL10 therapy