Site-Specific Antibody Conjugation for ADC and Beyond

被引:81
|
作者
Zhou, Qun [1 ]
机构
[1] Sanofi, Prot Engn, Biol Res, Framingham, MA 01701 USA
关键词
site-specific conjugation; specific amino acids; unnatural amino acids; glycans; short peptide tags; ADC; other applications; PROGRAMMED BISPECIFIC ANTIBODIES; HER2-POSITIVE BREAST-CANCER; ACUTE MYELOID-LEUKEMIA; UNNATURAL AMINO-ACIDS; ANAPLASTIC LARGE-CELL; DRUG CONJUGATE; TRASTUZUMAB EMTANSINE; BRENTUXIMAB VEDOTIN; THERAPEUTIC INDEX; TARGETED DELIVERY;
D O I
10.3390/biomedicines5040064
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antibody-drug conjugates (ADCs) have become a promising class of antitumor agents with four conjugates being approved by regulatory agencies for treating cancer patients. To improve the conventional conjugations that are currently applied to generate these heterogeneous products, various site-specific approaches have been developed. These methods couple cytotoxins or chemotherapeutic drugs to specifically defined sites in antibody molecules including cysteine, glutamine, unnatural amino acids, short peptide tags, and glycans. The ADCs produced showed high homogeneity, increased therapeutic index, and strong antitumor activities in vitro and in vivo. Moreover, there are recent trends in using these next generation technologies beyond the cytotoxin-conjugated ADC. These site-specific conjugations have been applied for the generation of many different immunoconjugates including bispecific Fab or small molecule-antibody conjugates, immunosuppressive antibodies, and antibody-antibiotic conjugates. Thus, it is likely that additional technologies and related site-specific conjugates will emerge in the near future, with various chemicals or small molecular weight proteins in addition to cytotoxin for better treatment of many challenging diseases.
引用
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页数:15
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