抗体与小分子药物一体化的完美_联姻_解析抗体_药物偶联物之定点偶联.pdf

PROGRESS IN PHARMACEUTICAL SCIENCES 2015,3399 4 :283-292 283    erfect Coupling of Antibodies with Small Molecule Drugs: P Site-specii c Conjugation for Antibody-Drug Conjugates LI Chenchen, WANG Min, ZHANG Juan (School of Life Science Technology, China Pharmaceutical University, Nanjing 210009, China) Antibody based targeted therapy has become more and more popular in anti-cancer therapy. Coupling of antibodies with small molecule drugs——antibody-drug conjugate(ADC) which is a new class of therapeutics has got a breakthrough. Conventional conjugation methods are based on lysine and cysteine residues and the ADCs yielded by these methods have poor stability. They are prone to aggregation and the conjugated drugs are easy to shed resulting in non-therapeutic side effects. The ADCs produced by the site-specifi c conjugation techniques developed recently have homogeneous drug-to-antibody ratios (DAR), similar pharmacokinetics with their parental antibodies and far less side effects than those of the conventional ADC with the same DAR. So the improved ADCs are expected to become a new generation of blockbuster drugs. Four site-specifi c conjugation methods for ADCs were reviewed herein. antibody-drug conjugate; site-specifi c conjugation; reactive cysteine; unnatural amino acid; enzyme-based method; disulfi de bond modifi cation