Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell.
Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell.
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Vγ2 x PD-L1，一种同时靶向 Vγ2 TCR 和 PD-L1 的双特异性抗体，可改善 Vγ2Vγ2 T 细胞的抗肿瘤反应
DOI：
10.3389/fimmu.2022.923969
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发表时间：
2022
影响因子：
7.3
通讯作者：
Zhou, Pengfei
中科院分区：
文献类型：
--
作者：
Yang, Rui;He, Qing;Zhou, Hui;Gong, Cheng;Wang, Xing;Song, Xingpan;Luo, Fang;Lei, Yang;Ni, Qian;Wang, Zili;Xu, Shasha;Xue, Yan;Zhang, Man;Wen, Haimei;Fang, Lijuan;Zeng, Liang;Yan, Yongxiang;Shi, Jian;Zhang, Jing;Yi, Jizu;Zhou, Pengfei
Vγ 2 VS 2 T细胞的有效细胞毒性特性使其对于过继性T细胞转移疗法具有吸引力。将扩增的Vγ 2 VS 2 T细胞移植到癌症患者中显示出良好的耐受性，但临床应答率需要提高，这意味着这种新型抗肿瘤疗法仍存在未满足的低毒性疗效。在这项研究中，我们测试了基于Y体的双特异性抗体（bsAb）Vγ2 x PD-L1的抗肿瘤功效，该抗体优先重定向Vγ 2 V δ2 T细胞以对抗PD-L1阳性肿瘤细胞。在对Vγ 2 VS 2 T细胞和PD-L1+肿瘤细胞具有纳摩尔亲和力水平的情况下，Vγ2 x PD-L1桥接Vγ 2 VS 2 T细胞与SKOV 3肿瘤细胞以形成细胞-细胞缀合。以PD-L1依赖性方式，bsAb增强扩增的Vγ 2 V δ2 T细胞的有效活化（CD 25 + CD 69+）、IFNγ释放、脱粒（CD 107 a+）和细胞因子产生（IFNγ+和TNFα+）。Vγ 2 VS 2 T细胞的激活消除了表达PD-L1的人癌细胞系，包括H1975、SK 0 V3、A375、H1299和H2228细胞，但不消除PD-L1阴性细胞，包括HEK-293（293）细胞和健康PBMC。最后，我们表明，将Vγ2 x PD-L1与过继转移Vγ 2 VS 2 T细胞组合抑制了现有肿瘤异种移植物的生长，并增加了进入肿瘤床的Vγ 2 VS 2 T细胞的数量。Vγ2 x PD-L1代表了一种有前途的试剂，可用于提高过继转移的Vγ 2 V δ2 T细胞在PD-L1阳性恶性肿瘤治疗中的疗效。
The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells. With nanomolar affinity levels to Vγ2Vδ2 T cells and PD-L1+ tumor cells, Vγ2 x PD-L1 bridges a Vγ2Vδ2 T cell with a SKOV3 tumor cell to form a cell-to-cell conjugation. In a PD-L1-dependent manner, the bsAb elicits effective activation (CD25+CD69+), IFNγ releasing, degranulation (CD107a+), and cytokine production (IFNγ+ and TNFα+) of expanded Vγ2Vδ2 T cells. The activations of the Vγ2Vδ2 T cells eliminate PD-L1-expressing human cancer cell lines, including H1975, SKOV3, A375, H1299, and H2228 cells, but not PD-L1 negative cells including HEK-293 (293) cells and healthy PBMCs. Finally, we show that combining Vγ2 x PD-L1 with adoptively transferring Vγ2Vδ2 T cells inhibits the growth of existing tumor xenografts and increases the number of Vγ2Vδ2 T cells into the tumor bed. Vγ2 x PD-L1 represents a promising reagent for increasing the efficacy of adoptively transferred Vγ2Vδ2 T cells in the treatment of PD-L1 positive malignant tumors.
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影响因子：
7.3
作者：
Lo Presti E;Dieli F;Meraviglia S
通讯作者：
Meraviglia S
影响因子：
11.4
作者：
Duell, J.;Dittrich, M.;Topp, M. S.
通讯作者：
Topp, M. S.
对PD-1和PD-L1阻滞的抗性机制。
DOI：
10.1097/ppo.0000000000000303
发表时间：
2018
期刊：
Cancer journal (Sudbury, Mass.)
影响因子：
--
作者：
Nowicki TS;Hu-Lieskovan S;Ribas A
通讯作者：
Ribas A
影响因子：
10.9
作者：
Alnaggar, Mohammed;Xu, Yan;Yin, Zhinan
通讯作者：
Yin, Zhinan
影响因子：
5.4
作者：
Pont, Frederic;Familiades, Julien;Fournie, Jean-Jacques
通讯作者：
Fournie, Jean-Jacques