用天然产品增强单克隆抗体:机制与应用

Madhan Gunasekaran , Sarvananda L , Amal D. Premarathna
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摘要

单克隆抗体(mab)已经彻底改变了广泛疾病的治疗策略,但其疗效仍然受到诸如次优肿瘤穿透和细胞毒性不足等挑战的限制。这项研究开创了一种综合方法,利用植物源性糖苷的未开发潜力和创新的生物技术进步来重新定义单克隆抗体的功效。具体来说,我们研究了用于增强免疫调节作用的β -葡聚糖类似物的新应用,不仅针对恶性细胞,还针对肿瘤微环境,以优化单抗的渗透。此外,我们引入了一种突破性的抗体-药物偶联物(adc)策略,利用以前未开发的天然毒素,如修饰的皂苷变体,这些毒素经过生物工程处理,以最小的脱靶效应实现选择性细胞毒性。这种新型ADC配方通过使用纳米胶囊技术进一步优化,确保在肿瘤环境中精确递送和控制释放。研究还集中在杂交表达系统,可扩展的单克隆抗体生产,靶向递送的纳米封装,以及用于改进抗体治疗的天然和合成技术的整合。通过将基于植物的表达系统与合成生物学工具相结合,创建了一个在产量和安全性方面超过传统植物或哺乳动物系统的混合平台。这种方法不仅降低了生产成本,而且还引入了一种可扩展的方法来快速适应单克隆抗体,以应对新出现的病原体或肿瘤突变。本研究通过混合天然和合成方法开辟了新的途径,最终提高了单克隆抗体在各种疾病状态下的治疗效果。它强调了将尖端技术与天然化合物相结合的变革潜力,为更有效、更有针对性和更适应性的基于抗体的治疗铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enhancing monoclonal antibodies with natural products: Mechanisms and applications
Monoclonal antibodies (mAbs) have revolutionized therapeutic strategies across a broad spectrum of diseases, yet their efficacy remains constrained by challenges such as suboptimal tumor penetration and insufficient cytotoxicity. This study pioneers an integrative approach, harnessing the untapped potential of plant-derived glycosides and innovative biotechnological advances to redefine mAb efficacy. Specifically, we investigate the novel application of beta-glucan analogs engineered for enhanced immunomodulatory effects, targeting not only malignant cells but also the tumor microenvironment to optimize mAb penetration. Moreover, we introduce a groundbreaking strategy in antibody-drug conjugates (ADCs) by leveraging previously unexploited natural toxins, such as modified saporin variants, which are bioengineered to achieve selective cytotoxicity with minimal off-target effects. This novel ADC formulation is further optimized through the use of nanoencapsulation techniques, ensuring precise delivery and controlled release within the tumor milieu. The research also focuses on hybrid expression systems, scalable mAb production, nanoencapsulation for targeted delivery, and the integration of natural and synthetic techniques for improved antibody therapies. By combining plant-based expression systems with synthetic biology tools, creating a hybrid platform that surpasses traditional plant or mammalian systems in both yield and safety. This approach not only reduces production costs but also introduces a scalable method for the rapid adaptation of mAbs in response to emerging pathogens or tumor mutations. This study opens new avenues by blending natural and synthetic methodologies, ultimately enhancing the therapeutic outcomes of mAbs across various disease states. It underscores the transformative potential of integrating cutting-edge technologies with natural compounds, paving the way for more effective, targeted, and adaptable antibody-based therapies.
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