Verhoeyen M, Milstein C, Winter G
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Science. 1988 Mar 25;239(4847):1534-6. doi: 10.1126/science.2451287.
The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the "humanizing" of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.
事实证明，利用杂交瘤技术生产治疗性人源单克隆抗体存在困难，这促使人们通过重组DNA技术对小鼠单克隆抗体进行“人源化”。此前研究表明，通过移植高变环，可将小鼠抗体重链可变结构域中的一个小分子半抗原结合位点嫁接到人骨髓瘤蛋白的相应位点上。现在有研究表明，蛋白质抗原（溶菌酶）的一个大结合位点也能从小鼠重链移植到人重链上。这种结构构建的成功可能得益于诱导契合机制。
