Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
Biomed Res Int. 2020 Mar 3;2020:3415471. doi: 10.1155/2020/3415471. eCollection 2020.
polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-display technology was utilized to isolate specific anti-programmed death-1 (PD-1) antibodies from mice stimulated by APS and to confirm whether the isolated anti-PD-1 antibody could inhibit the interaction of PD-1 with the programmed death-ligand 1 (PD-L1), resulting in tumor growth inhibition. The isolated single-chain fragment variable (scFv) S12 exhibited the highest binding affinity of 20 nM to PD-1, completed the interaction between PD-1 and PD-L1, and blocked the effect of PD-L1-induced T cell exhaustion in peripheral blood mononuclear cells in vitro. In the animal model, the tumor growth inhibition effect after scFv S12 treatment was approximately 48%. However, meaningful synergistic effects were not observed when scFv S12 was used as a cotreatment with ixabepilone. Moreover, this treatment caused a reduction in the number of tumor-associated macrophages in the tumor tissue. These experimental results indirectly indicate the ability of APS to induce specific antibodies associated with the immune checkpoint system and the potential benefits for improving immunity in humans.
多糖 (APS) 成分是中药的主要成分，已被证明能激活 T 细胞和 B 细胞，增强人体免疫力。在这项研究中，给小鼠接种 APS 后，发现细胞因子和抗 PD-1 抗体滴度升高。因此，利用噬菌体展示技术从 APS 刺激的小鼠中分离出特异性抗程序性死亡受体 1 (PD-1) 抗体，并确认分离出的抗 PD-1 抗体是否能抑制 PD-1 与程序性死亡配体 1 (PD-L1) 的相互作用，从而抑制肿瘤生长。分离出的单链可变片段 (scFv) S12 对 PD-1 的结合亲和力最高，达 20nM，完成了 PD-1 与 PD-L1 的相互作用，并阻断了 PD-L1 在体外诱导外周血单个核细胞中 T 细胞耗竭的作用。在动物模型中，scFv S12 治疗后肿瘤生长抑制作用约为 48%。然而，当 scFv S12 与伊沙匹隆联合治疗时，并未观察到有意义的协同作用。此外，这种治疗方法还导致肿瘤组织中肿瘤相关巨噬细胞数量减少。这些实验结果间接表明 APS 诱导与免疫检查点系统相关的特异性抗体的能力，以及改善人类免疫力的潜在益处。
