抗體–藥物偶聯(lián)（ADC）是現(xiàn)代“精準醫(yī)療”需求下藥學發(fā)展的必然趨勢。從2000年第一款ADC藥物的上市成功到2020年ADC藥物的研發(fā)層出不窮。腫瘤靶向治療的發(fā)展帶動了ADC藥物研發(fā)領域的快速興起。ADC藥物是使用具有特異性的單克隆抗體與具有生物活性的細胞毒素結合，將藥物特異性遞送至腫瘤表面位點，避免對正常細胞的殺傷，減少毒副作用。ADC為細胞毒性有效載荷提供了一種較為理想的遞送方法。但是也必須清楚的認識到，由于腫瘤異質性、腫瘤代謝、腫瘤血供等多種因素導致的腫瘤耐藥是ADC藥物發(fā)展中所面臨的一大挑戰(zhàn)。從ADC藥物的發(fā)展進程、臨床應用及其所面臨的耐藥問題進行綜述，探討抗體偶聯(lián)藥物的臨床應用及其所面臨的挑戰(zhàn)和策略。

Antibody-drug conjugates (ADC) is one of the inevitable pharmaceutical developments meets the demand of modern "precision medicine". Since the success of the first ADC drug had been listed in 2000, there has been an endless stream of ADC research and development during two decades. The development of tumor targeted therapy has led to the rapid rise in the field of ADC. ADC uses specific monoclonal antibodies to combine with bioactive cytotoxins to deliver specific drugs to tumor surface sites, in order to avoid killing normal cells and decreasing side effects. ADC provides an ideal delivery method for cytotoxic payloads. However, we must also clearly recognize that tumor drug resistance caused by tumor heterogeneity, tumor metabolism, tumor blood supply, and other elements is a major challenge in the development of ADC drugs. We review the development, clinical application, and drug resistance problems of ADC, and discuss the clinical application, challenges, and strategies of ADC.

R979.1

國家自然科學基金面上項目（81972252）；國家自然科學基金青年項目（81703401）；上海市衛(wèi)健委2021年面上項目（202040382）