A new PD-1-specific nanobody enhances the antitumor activity of T-cells in synergy with dendritic cell vaccine
A new PD-1-specific nanobody enhances the antitumor activity of T-cells in synergy with dendritic cell vaccine
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新型 PD-1 特异性纳米抗体与树突状细胞疫苗协同增强 T 细胞的抗肿瘤活性
DOI：
10.1016/j.canlet.2021.09.028
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发表时间：
2021
期刊：
影响因子：
9.7
通讯作者：
Lu Xiaoling
中科院分区：
文献类型：
--
作者：
Shi Wei;Yang Xiaomei;Xie Shenxia;Zhong Dani;Lin Xu;ong;Ding Ziqiang;Duan Siliang;Mo Fengzhen;Liu Aiqun;Yin Shihua;Jiang Xiaobing;Xu Zhi Ping;Lu Xiaoling
尽管PD-1阻断在癌症治疗中取得了许多成功和机会，但抗PD-1单克隆抗体仍面临多重挑战。在此，我们报告了一种基于纳米抗体（Nb）的策略来规避这些障碍。一种新的PD-1阻断Nb（PD-1 Nb 20）与肿瘤特异性树突状细胞（DC）/肿瘤融合细胞（FC）疫苗的组合，旨在改善CD 8 + T细胞的活化、增殖、细胞因子分泌和肿瘤细胞毒性。发现该组合有效地增强了CD 8 + T细胞的体外细胞毒性，以杀死人非小细胞肺癌（NSCLC）HCC 827细胞、肝细胞癌（HCC）HepG 2细胞和舌鳞状细胞癌（TSCC）Tca 8113细胞。此外，用PD-1 Nb 20和肿瘤特异性DC/肿瘤-FC预处理的CD 8 + T细胞通过促进T细胞浸润以杀死肿瘤细胞和抑制肿瘤血管生成，显著抑制NSCLC、HCC和TSCC衍生的异种移植肿瘤的生长，并延长荷瘤小鼠的存活。这些数据表明，PD-1 Nb 20与DC/肿瘤FC疫苗协同作用增强了CD 8 + T细胞的广谱抗肿瘤活性，为T细胞功能障碍或对抗PD-1治疗不敏感的肿瘤患者提供了替代和有前景的免疫策略。
Despite the many successes and opportunities presented by PD-1 blockade in cancer therapies, anti-PD-1 monoclonal antibodies still face multiple challenges. Herein we report a strategy based on a nanobody (Nb) to circumvent these obstacles. A new PD-1-blocking Nb (PD-1 Nb20) in combination with tumor-specific dendritic cell (DC)/tumor-fusion cell (FC) vaccine that aims to improve the activation, proliferation, cytokine secretion, and tumor cell cytotoxicity of CD8+T-cells. This combination was found to effectively enhance thein vitrocytotoxicity of CD8+T-cells to kill human non-small cell lung cancer (NSCLC) HCC827 cells, hepatocellular carcinoma (HCC) HepG2 cells, and tongue squamous cell carcinoma (TSCC) Tca8113 cells. Moreover, CD8+T-cells pre-treated with PD-1 Nb20 and tumor-specific DC/tumor-FCs significantly suppressed the growth of NSCLC-, HCC- and TSCC-derived xenograft tumors and prolonged the survival of tumor-bearing mice, through promoting T-cell infiltration to kill tumor cells and inhibiting tumor angiogenesis. These data demonstrate that PD-1 Nb20 in synergy with DC/tumor-FC vaccine augment the broad spectrum of antitumor activity of CD8+T-cells, providing an alternative and promising immunotherapeutic strategy for tumor patients who are T-cell-dysfunctional or not sensitive to anti-PD-1 therapy.