1890年馮˙貝林(von Behring)發(fā)現(xiàn)了抗白喉毒素血清,發(fā)明了人工被動免疫,并提出了抗原和抗體的概念,在后續(xù)漫長的抗體研究中,人類相繼發(fā)展出三代抗體制備技術(shù):
①第一代抗體:以抗原免疫高等脊椎動物制備的多克隆抗體;
②第二代抗體:由雜交瘤技術(shù)產(chǎn)生的只針對某一種特定抗原決定簇的單克隆抗體;
③第三代抗體:應用分子克隆技術(shù)、基因突變技術(shù)改造某種抗體的基因編碼序列,生產(chǎn)出的性能更優(yōu)越的抗體,也稱為基因工程抗體或重組抗體。
單抗的出現(xiàn)及其顯著的優(yōu)越性(特異性高、蛋白類天然產(chǎn)物等特性)使其在疾病的研究、診斷和治療中得到廣泛應用,但也受到人體的強烈排斥。第三代抗體的產(chǎn)生在一定程度上解決了由于鼠單抗的異源性導致的排斥反應。
從最初的人-鼠嵌合抗體將人源化比例升到60~70%,到通過CDR嫁接技術(shù)產(chǎn)生的人源化比例更高的人源化抗體,再到由噬菌體展示技術(shù)獲得的全人抗體,技術(shù)的發(fā)展不斷提高著抗體的質(zhì)量及人類對抗疾病的能力。除此之外,基因工程除了可獲得全長抗體,還可獲得抗體片段——小分子抗體,例如單鏈抗體、Fab片段等。這些小分子抗體由于其獨特的分子量小、組織滲透性強等特點,也被廣泛應用于臨床診斷及治療。
In 1890 Von Behring discovered the antidiphtheria toxin serum, invented artificial passive immunity, and came up with the concept of Antigen and antibody, three generations of antibody preparation techniques have been developed: 1 THE FIRST GENERATION OF ANTIBODIES: polyclonal antibodies prepared by Antigen Immunization with Vertebrata; SECOND GENERATION ANTIBODIES: ANTIBODIES PRODUCED BY hybridoma techniques that target a specific Epitope monoclonal antibody; Third Generation Antibodies: The use of molecular cloning techniques, genetic mutations to modify the genetic coding sequence of an antibody, the production of better performance of antibodies, also known as genetically engineered antibodies or recombinant antibodies. Monoclonal antibody (mcab) has been widely used in the research, diagnosis and treatment of diseases because of its high specificity, natural products of protein and so on. The generation of the third generation antibody solved the rejection reaction caused by the heterologous nature of mouse monoclonal antibody to some extent. From initial human-mouse chimeric antibodies that humanize 60 to 70 percent, to more humanized antibodies produced by CDR grafting, to whole human antibodies obtained by Phage display, technology continues to improve the quality of antibodies and the ability of humans to fight disease. In addition, in addition to the full-length antibody, the antibody fragments, such as single chain antibody and Fab fragment, can also be obtained by genetic engineering. These small-molecule antibodies are widely used in clinical diagnosis and treatment because of their unique characteristics such as small molecular weight and strong tissue permeability.