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抗体药物偶联物在癌症治疗中的应用:创新、挑战与未来方向。

Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions.

机构信息

Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India.

Institute of Pharmaceutical Research, GLA University, Mathura, U.P., India.

出版信息

Arch Pharm Res. 2024 Jan;47(1):40-65. doi: 10.1007/s12272-023-01479-6. Epub 2023 Dec 28.

Abstract

The emergence of antibody-drug conjugates (ADCs) as a potential therapeutic avenue in cancer treatment has garnered significant attention. By combining the selective specificity of monoclonal antibodies with the cytotoxicity of drug molecules, ADCs aim to increase the therapeutic index, selectively targeting cancer cells while minimizing systemic toxicity. Various ADCs have been licensed for clinical usage, with ongoing research paving the way for additional options. However, the manufacture of ADCs faces several challenges. These include identifying suitable target antigens, enhancing antibodies, linkers, and payloads, and managing resistance mechanisms and side effects. This review focuses on the strategies to overcome these hurdles, such as site-specific conjugation techniques, novel antibody formats, and combination therapy. Our focus lies on current advancements in antibody engineering, linker technology, and cytotoxic payloads while addressing the challenges associated with ADC development. Furthermore, we explore the future potential of personalized medicine, leveraging individual patients' molecular profiles, to propel ADC treatments forward. As our understanding of the molecular mechanisms driving cancer progression continues to expand, we anticipate the development of new ADCs that offer more effective and personalized therapeutic options for cancer patients.

摘要

抗体药物偶联物 (ADC) 在癌症治疗中作为一种潜在的治疗途径已经引起了广泛关注。通过将单克隆抗体的选择性特异性与药物分子的细胞毒性相结合,ADC 旨在提高治疗指数,选择性地靶向癌细胞,同时最大限度地减少全身毒性。已经有多种 ADC 获得了临床应用许可,并且正在进行的研究为更多的选择铺平了道路。然而,ADC 的制造面临着一些挑战。这些挑战包括确定合适的靶抗原、增强抗体、连接子和有效载荷,并管理耐药机制和副作用。本综述重点讨论了克服这些障碍的策略,例如定点偶联技术、新型抗体形式和联合治疗。我们专注于当前在抗体工程、连接子技术和细胞毒性有效载荷方面的进展,同时解决 ADC 开发所面临的挑战。此外,我们还探讨了个性化医疗的未来潜力,利用个体患者的分子谱来推动 ADC 治疗的发展。随着我们对推动癌症进展的分子机制的理解不断深入,我们预计将开发出更有效和个性化的治疗选择,为癌症患者提供更好的治疗效果。

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