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Cancer Sci. 2008 Feb;99(2):361-7. doi: 10.1111/j.1349-7006.2007.00664.x. Epub 2008 Jan 14.

Anti-OX40 monoclonal antibody therapy in combination with radiotherapy results in therapeutic antitumor immunity to murine lung cancer.

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1
First Department of Medicine, Hokkaido University, School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-0815, Japan. yokouchi@med.hokudai.ac.jp

Abstract

The therapeutic effect of agonistic anti-OX40 (CD134) monoclonal antibody (mAb) in combination with radiotherapy was evaluated in a murine lung cancer model. After intradermal transplantation of ovalbumin (OVA)-transfected Lewis lung carcinoma, C57BL/6 mice were irradiated locally with a single dose of 20 Gy in combination with an intratumoral injection of anti-OX40 mAb at 50 microg on day 4 after transplantation, which is when the major axis of the inoculated tumor reached a diameter of 7-9 mm. On days 8, 11, and 14, the tumor-bearing mice were further treated with the same dose of anti-OX40 mAb. Anti-OX40 mAb in combination with radiotherapy prolonged survival and provided greater efficacy than either single treatment against well-established tumors. An in vivo depletion study suggested that therapeutic immunity was mainly CD8(+) T-cell dependent. OX40(+)CD8(+) T cells were augmented in draining lymph nodes obtained from irradiated mice compared with those from non-irradiated mice. OVA-major histocompatibility complex tetramer(+) CD8(+) T cells had been strongly recruited to the draining lymph nodes obtained from mice treated with anti-OX40 mAb in combination with radiotherapy, and strong antigen-specific cytotoxicity was confirmed by a (51)Cr-release assay. Moreover, a tumor-rechallenge model indicated that this combination therapy induced durable tumor immunity. Thus, anti-OX40 mAb in combination with radiotherapy may potentially help the management of patients with lung cancer.

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