抗体药物偶联物(antibody drug conjugates,ADC)是一类具有良好靶向性的抗肿瘤药物,它利用单克隆抗体与高效细胞毒分子的完美结合,最大程度地增加了高效细胞毒分子的治疗窗。近年来,随着Adcetris和Kadcyla两个ADC药物的相继上市,抗体药...抗体药物偶联物(antibody drug conjugates,ADC)是一类具有良好靶向性的抗肿瘤药物,它利用单克隆抗体与高效细胞毒分子的完美结合,最大程度地增加了高效细胞毒分子的治疗窗。近年来,随着Adcetris和Kadcyla两个ADC药物的相继上市,抗体药物偶联物的研究也逐渐成为靶向抗肿瘤治疗领域的一个研究热点。本文对ADC主要组成部件研究进展及上市ADC药物Kadcyla和美登素相关ADC药物的临床试验状况进行综述,并对未来ADC发展趋势进行展望,希望为今后的ADC药物研究工作提供的参考和借鉴。展开更多
The clinical translation of nanomedicine is hindered by the low delivery efficiency, and consequently drug concentration in tumor sites falls short of the therapeutic effective range which leads to poor clinical outco...The clinical translation of nanomedicine is hindered by the low delivery efficiency, and consequently drug concentration in tumor sites falls short of the therapeutic effective range which leads to poor clinical outcomes. One important lesson learned from the development of antibody-drug-conjugates (ADCs) is that to achieve significant clinical benefits, extremely potent cytotoxic agents and cleavable linkers should be used. By encapsulating maytansinoid, AP3, which is 100-1,000 times more potent than most conventional small molecule anticancer drugs, in pH-sensitive acetalated dextran-polyethylene glycol (PEG)(ADP) nanocarriers, even with only 1% drug loading, we were able to eradicate tumors in 50% of tested animals with negligible side effects, while free AP3 only showed marginal efficacy and severe liver damages. This study suggests that besides improving the low efficiency of nano-delivery systems, the potency of drug to be delivered is also critical to the clinical outcomes of nanomedicine. Our results also showed that ADP nanoparticles (NPs) were able to expand the narrow therapeutic window of maytansinoids in a similar manner to the ADCs.展开更多
文摘抗体药物偶联物(antibody drug conjugates,ADC)是一类具有良好靶向性的抗肿瘤药物,它利用单克隆抗体与高效细胞毒分子的完美结合,最大程度地增加了高效细胞毒分子的治疗窗。近年来,随着Adcetris和Kadcyla两个ADC药物的相继上市,抗体药物偶联物的研究也逐渐成为靶向抗肿瘤治疗领域的一个研究热点。本文对ADC主要组成部件研究进展及上市ADC药物Kadcyla和美登素相关ADC药物的临床试验状况进行综述,并对未来ADC发展趋势进行展望,希望为今后的ADC药物研究工作提供的参考和借鉴。
文摘The clinical translation of nanomedicine is hindered by the low delivery efficiency, and consequently drug concentration in tumor sites falls short of the therapeutic effective range which leads to poor clinical outcomes. One important lesson learned from the development of antibody-drug-conjugates (ADCs) is that to achieve significant clinical benefits, extremely potent cytotoxic agents and cleavable linkers should be used. By encapsulating maytansinoid, AP3, which is 100-1,000 times more potent than most conventional small molecule anticancer drugs, in pH-sensitive acetalated dextran-polyethylene glycol (PEG)(ADP) nanocarriers, even with only 1% drug loading, we were able to eradicate tumors in 50% of tested animals with negligible side effects, while free AP3 only showed marginal efficacy and severe liver damages. This study suggests that besides improving the low efficiency of nano-delivery systems, the potency of drug to be delivered is also critical to the clinical outcomes of nanomedicine. Our results also showed that ADP nanoparticles (NPs) were able to expand the narrow therapeutic window of maytansinoids in a similar manner to the ADCs.
