抗體藥物偶聯(lián)物(ADC)已經(jīng)成為一種重要的藥物類別,，它是一種利用抗體的特異性，并結(jié)合有治療作用的小分子治療劑的藥物,。 ADC的三個(gè)主要組成元件包括：抗體,，連接子，和效應(yīng)分子,。早期研發(fā)工作多數(shù)集中在改善這些效應(yīng)分子的功能,。目前，研發(fā)方向開始已集中如何控制連接子/藥物在與抗體偶聯(lián)時(shí)的位點(diǎn)和數(shù)量,，以產(chǎn)生更均勻的ADC,。
近日，在《美國藥學(xué)科學(xué)家協(xié)會》雜志(The AAPS journal)上發(fā)表了一篇綜述,，對目前廣泛使用的偶聯(lián)方法,，以及近期出現(xiàn)的新方法，包括“點(diǎn)擊”偶聯(lián)和酶連接進(jìn)行了綜述。該綜述發(fā)表于2015年3月,。
該綜述討論當(dāng)前的接頭技術(shù),，對比了可裂解連接子和不可裂解連接子的性質(zhì)，并圍繞藥物治療總結(jié)了ADC的有效載藥量的基本屬性,。此外,，還總結(jié)了確定ADC的物理化學(xué)性質(zhì)的測定方法，以及獲得均勻產(chǎn)品的純化方法,。最后,，研究者認(rèn)為建立一套ADC的元件選擇和分析標(biāo)準(zhǔn)，將有利于新型ADC藥物的轉(zhuǎn)化,，并保證產(chǎn)物的生物有效性,。
參考文獻(xiàn)：McCombs et al.The AAPS journal 2015;17(2):339-351
英文鏈接：Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry .
http://link.springer.com/article/10.1208/s12248-014-9710-8
原文摘要：
Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry.
Antibodydrug conjugates (ADCs) have emerged as an important pharmaceutical class of drugs designed to harness the specificity of antibodies with the potency of small molecule therapeutics. The three main components of ADCs are theantibody, the linker, and the payload; the majority of early work focused intensely on improving the functionality of these pieces. Recently, considerable attention has been focused on developing methods to control the site and number of linker/drug conjugated to theantibody, with the aim of producing more homogenous ADCs. In this article, we review popular conjugation methods and highlight recent approaches including "click" conjugation and enzymatic ligation. We discuss current linker technology, contrasting the characteristics of cleavable and non-cleavable linkers, and summarize the essential properties ofADCpayload, centering on chemotherapeutics. In addition, we report on the progress in characterizing to determine physicochemical properties and on advances in purifying to obtain homogenous products. Establishing a set of selection and analytical criteria will facilitate the translation of novel ADCs and ensure the production of effective biosimilars.
