报告题目: Cancer immunotherapy harnessing PD-1 immune checkpoint inhibitors and γδT cells

报告人  : Yoshimasa Tanaka 教授，日本长崎大学

报告时间: 2019年4月25日12:30-14:00

报告地点: 生科院二楼大会议室

邀请人  : 苏莉 教授

报告专家简介：

Yoshimasa Tanaka 教授，长崎大学生物医学科学研究科生物信息学和分子医学中心主任，同时任职于京都大学大学院医学研究科免疫调节技术与治疗创新中心。他的研究工作包括鉴定异戊烯焦磷酸及其类似物作为表达Vγ2Vδ2 TCR的γδT细胞刺激物、开发利用PD-1免疫检查点阻断的癌症免疫疗法、过继转移人γδT细胞用于肾细胞癌患者的癌症免疫治疗、开发具有强效抗肿瘤活性的新型双膦酸盐前药、以及联合使用IL-18增强癌症免疫疗法。在Nature，Science，Immunity，PNAS等期刊上发表多篇论文。

报告摘要：

Standard cancer treatments comprise surgery, radiotherapy, chemotherapy, hormone therapy and targeted therapy. Recently, immunotherapy has become a clinically validated intervention for cancer patients since PD-1 and CTLA-4 immune checkpoint therapies were introduced. We first established an anti-mouse PD-L1 monoclonal antibody (mAb) and demonstrated that the mAb was effective in augmenting anti-tumor activity in vitro as well as in vivo in animal experimental models. We also showed that anti-human PD-L1 mAb augmented anti-tumor activity in human Vg2Vd2⁺ (also termed Vg9Vd2⁺) gdT cells that specifically recognize metabolites in the mevalonate pathway. The PD-1 immune checkpoint therapy was later confirmed to be efficacious in patients with melanoma, lung cancer and kidney cancer.

It is, however, imperative to develop alternatives to immune checkpoint therapy, because the efficacy of the immune checkpoint therapy is at best 20%~30% and some patients suffer from treatment-related adverse events including pneumonitis, hypothyroidism, colitis and hepatitis. One of the most promising immunotherapies is an adoptive transfer of immune effector cells that specifically recognize malignant tumors. We synthesized a series of N-BPs that were specifically recognized by Vg2Vd2⁺ gdT cells, and analyzed the effect of the compounds on the cell-mediated cytotoxicity and the expansion of Vg2Vd2⁺ gdT cells.