Barreca Marilia, Lang Noémie, Tarantelli Chiara, Spriano Filippo, Barraja Paola, Bertoni Francesco
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90123 Palermo, Italy.
Division of Oncology, Department of Oncology, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland.
Explor Target Antitumor Ther. 2022;3(6):763-794. doi: 10.37349/etat.2022.00112. Epub 2022 Dec 26.
Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper it provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed.
抗体药物偶联物(ADCs)是一种用于恶性肿瘤治疗的最新革命性方法,与全身细胞毒性化疗相比,旨在提供卓越的疗效和对肿瘤细胞的特异性靶向作用。它们的结构通过化学连接子将高效抗癌药物(载荷或弹头)与针对肿瘤相关抗原的单克隆抗体(Abs)结合在一起。由于单克隆抗体具有灵敏的靶向能力,能够将细胞毒性载荷直接递送至肿瘤细胞,这些药物不会伤害健康细胞,从而降低了毒性。不同的ADC已获得美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)的批准,可作为单一疗法或与化疗联合用于治疗多种恶性疾病,包括淋巴瘤患者。全球有超过100种ADC正在进行临床前和临床研究。本文概述了在淋巴瘤治疗临床开发中已获批准且前景广阔的ADC。讨论了ADC设计的每个组成部分、它们的作用机制以及临床开发进展的要点。