Division of Cell Biology, Bio-Medical Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Biochem Biophys Res Commun. 2010 Mar 19;393(4):829-35. doi: 10.1016/j.bbrc.2010.02.092. Epub 2010 Feb 18.
CD27 plays an important role in T-cell co-stimulation and is also expressed on lymphomas. In the present study, we generated novel depleting and non-depleting monoclonal antibodies (mAbs) against mouse CD27 and characterized their co-stimulatory activity in vitro and anti-tumor effects in immune-competent mice bearing syngeneic T-cell lymphoma (EG7) expressing or lacking CD27. A profound anti-tumor effect was observed with a non-depleting mAb (RM27-3E5), but not with a depleting mAb (RM27-3C1), against either EG7/CD27(+) or EG7/CD27(-) tumors, which was associated with the induction of EG7-specific cytotoxic T lymphocytes (CTLs). Consistently, the anti-tumor effect of RM27-3E5 was abolished in T cell-deficient nude mice. These results indicate that a non-depleting agonistic mAb against CD27 is promising for cancer therapy by co-stimulating tumor-specific CTL induction.
CD27 在 T 细胞共刺激中发挥重要作用，也在淋巴瘤上表达。在本研究中，我们针对小鼠 CD27 生成了新型的耗竭型和非耗竭型单克隆抗体（mAb），并在体外表征了它们的共刺激活性，以及在表达或缺乏 CD27 的同源 T 细胞淋巴瘤（EG7）的免疫功能正常的小鼠中评估了它们的抗肿瘤效果。我们发现，一种非耗竭型 mAb（RM27-3E5）对 EG7/CD27(+)或 EG7/CD27(-)肿瘤具有显著的抗肿瘤作用，而耗竭型 mAb（RM27-3C1）则没有，这与诱导 EG7 特异性细胞毒性 T 淋巴细胞（CTL）有关。一致地，在 T 细胞缺陷的裸鼠中，RM27-3E5 的抗肿瘤作用被消除。这些结果表明，针对 CD27 的非耗竭型激动型 mAb 通过共刺激肿瘤特异性 CTL 的诱导，有望用于癌症治疗。
