Anti-OX40 monoclonal antibody therapy in combination with radiotherapy results in therapeutic antitumor immunity to murine lung cancer
Anti-OX40 monoclonal antibody therapy in combination with radiotherapy results in therapeutic antitumor immunity to murine lung cancer
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DOI：
10.1111/j.1349-7006.2007.00664.x
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发表时间：
2008-02-01
期刊：
影响因子：
5.7
通讯作者：
Nishimura, Masaharu
中科院分区：
文献类型：
--
作者：
Yokouchi, Hiroshi;Yamazaki, Koichi;Nishimura, Masaharu
在小鼠肺癌模型中评估了激动性抗OX 40（CD 134）单克隆抗体（mAb）与放疗联合的治疗效果。在卵清蛋白（OVA）转染的刘易斯肺癌皮内移植后，在移植后第4天，即当接种肿瘤的长轴达到7-9 mm直径时，用20戈伊的单次剂量局部照射C57 BL/6小鼠，并结合瘤内注射50 μ g抗-OX 40 mAb。进一步用相同剂量的抗OX 40 mAb处理荷瘤小鼠。抗OX 40 mAb与放疗联合使用可延长生存期，并比任何一种单一治疗对已确定的肿瘤提供更大的疗效。一项体内耗竭研究表明，治疗性免疫主要依赖于CD 8（+）T细胞。OX 40（+）CD 8（+）T细胞在受照小鼠引流淋巴结中的表达明显高于未受照小鼠。OVA-主要组织相容性复合物四聚体（+）CD 8（+）T细胞已被强烈募集到从抗OX 40 mAb联合放疗处理的小鼠获得的引流淋巴结中，并且通过Cr-51释放试验证实了强的抗原特异性细胞毒性。此外，肿瘤再激发模型表明，这种联合治疗诱导持久的肿瘤免疫。因此，抗OX 40 mAb与放疗联合可能有助于肺癌患者的治疗。
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 mu g 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 Cr-51-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.