Bulaon Christine Joy I, Sun Hongyan, Malla Ashwini, Phoolcharoen Waranyoo
Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Biotechnol Rep (Amst). 2023 Mar 28;38:e00794. doi: 10.1016/j.btre.2023.e00794. eCollection 2023 Jun.
The therapeutic blockade of inhibitory PD-1 signaling has emerged as an effective approach for cancer immunotherapy. Nivolumab (Opdivo®), a monoclonal antibody (mAb) targeting the PD-1 immune checkpoint, is approved for treatment of several cancer indications. It functions by blocking the PD-1-mediated T-cell inhibition thus reinstating anticancer immune responses. Tremendous advances in plant biotechnology offer an alternative and economical strategy to produce therapeutic mAbs for immune-based therapies. In this study, recombinant anti-PD-1 Nivolumab was produced in and the plant-produced anti-PD-1 mAb was exploited for cancer treatment in syngeneic mice model C57BL/6 mice that were used to test the antitumor efficacy of plant produced Nivolumab, along with commercial Opdivo®. C57BL/6 syngeneic mice treated with plant produced anti-PD-1 mAb exhibited reduction in the growth of established MC38 tumors. The plant produced Nivolumab treatment showed 82.9% antitumor effect in decreasing the tumor volume along with 50% tumor-free mice, whereas Opdivo® showed 90.26% reduction in volume without any tumor-free mice. Finally, plant-derived anti-PD-1 therapy was also well tolerated in tumor-bearing mice that correlated with no significant body weight changes. Overall, our plant-produced Nivolumab elicits significant inhibition of tumor growth and provides a proof-of-concept for the production of immunotherapy targeting PD-1.
抑制性PD-1信号通路的治疗性阻断已成为癌症免疫治疗的一种有效方法。纳武单抗（欧狄沃®）是一种靶向PD-1免疫检查点的单克隆抗体（mAb），已被批准用于治疗多种癌症适应症。它通过阻断PD-1介导的T细胞抑制作用来恢复抗癌免疫反应。植物生物技术的巨大进步为生产用于免疫治疗的治疗性单克隆抗体提供了一种替代且经济的策略。在本研究中，在[具体植物]中生产了重组抗PD-1纳武单抗，并利用植物产生的抗PD-1单克隆抗体在同基因小鼠模型C57BL/6小鼠中进行癌症治疗，该模型用于测试植物产生的纳武单抗与市售欧狄沃®的抗肿瘤疗效。用植物产生的抗PD-1单克隆抗体治疗的C57BL/6同基因小鼠显示已建立的MC38肿瘤生长受到抑制。植物产生的纳武单抗治疗在减少肿瘤体积方面显示出82.9%的抗肿瘤效果，同时有50%的无瘤小鼠，而欧狄沃®显示体积减少90.26%但无无瘤小鼠。最后，植物源抗PD-1疗法在荷瘤小鼠中也具有良好的耐受性，这与体重无显著变化相关。总体而言，我们植物产生的纳武单抗能显著抑制肿瘤生长，并为生产靶向PD-1的免疫疗法提供了概念验证。
