Angiopoietin-2 blocking antibodies improve tumor growth inhibition and survival in mice treated with low doses of radiation

Almost 50 % of all cancer patients receive radiation therapy during their treatment, yet several tumor types show radiation therapy resistance that compromises treatment efficacy. Many radiation sensitizers have been tested for improvement of the outcome of radiation therapy. For example, inhibitors of VEGF and VEGF receptors were tested in attempt to normalize the tumor vasculature and to improve the outcome of radiation therapy. Here, we have analysed if antibodies blocking the angiogenic factor angiopoietin-2 could improve radiation therapy of mouse tumor isografts and human tumor xenografts in mice. To test if the anti-tumor effect of small doses of radiation can be increased by Ang2 blocking antibodies, we analysed the radiation sensitivity of subcutaneous tumor isografts in C57bl/6JRj mice, and human xenografts in NOD scid gamma mice. In several models, the combination treatment with anti-Ang2 plus radiation was superior to the monotherapies in decreasing tumor growth and increasing the lifespan of the tumor-bearing mice both in immunocompetent and immunocompromised mice. Based on our results, the anti-Ang2 blocking antibody treatment could be tested in the clinics to improve the effect of radiation therapy, especially in those cases in which an optimal radiation dose cannot be given because of the radiation sensitivity of the surrounding tissues. Citation Format: Pauliina Kallio, Elina Jokinen, Suvendu Das, Jenny Hogstrom, Sarika Heino, Marianne Lahde, Kari Alitalo. Angiopoietin-2 blocking antibodies improve tumor growth inhibition and survival in mice treated with low doses of radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 861.