基于美登素类和奥瑞他汀类抗体药物偶联物的物理特性比较
Physical characteristics comparison between maytansinoid-based and auristatin-based antibody-drug conjugates.
作者信息
Fujii Tomohiro, Reiling Calliste, Quinn Colette, Kliman Michal, Mendelsohn Brian A, Matsuda Yutaka
机构信息
Ajinomoto Bio-Pharma Services, 11040 Roselle Street, San Diego, CA 92121, United States.
TA Instruments, 159 Lukens Drive, New Castle, DE 19720, United States.
出版信息
Explor Target Antitumor Ther. 2021;2(6):576-585. doi: 10.37349/etat.2021.00064. Epub 2021 Dec 31.
AIM
Direct analytical comparison of two major drug-linkers in the antibody-drug conjugate (ADC) field was conducted.
METHODS
Four different analytical methods [AlogP calculation, reverse phase (RP) high-performance liquid chromatography (HPLC; RP-HPLC), size exclusion chromatography HPLC (SEC-HPLC), and differential scanning calorimetry (DSC)] were tested for this comparison.
RESULTS
Maytansinoid-based ADCs showed less hydrophobicity than auristatin-based ADCs. Regardless of the drug-linker and drug-to-antibody ratios (DARs), the stability detected by DSC was decreased by conjugation.
CONCLUSIONS
The cost and time-efficient analytical comparison described in this manuscript may be useful information for an initial characterization of ADCs prior to detailed biological studies.
目的
对抗体药物偶联物（ADC）领域的两种主要药物连接子进行直接分析比较。
方法
为此比较测试了四种不同的分析方法[LogP计算、反相（RP）高效液相色谱（HPLC；RP-HPLC）、尺寸排阻色谱HPLC（SEC-HPLC）和差示扫描量热法（DSC）]。
结果
基于美登素的ADC比基于奥瑞他汀的ADC疏水性更低。无论药物连接子和药物与抗体比率（DAR）如何，通过DSC检测到的稳定性因偶联而降低。
结论
本手稿中描述的成本效益高且省时的分析比较可能是在进行详细生物学研究之前对ADC进行初步表征的有用信息。
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