Shearman C W, Kanzy E J, Lawrie D K, Li Y W, Thammana P, Moore G P, Kurrle R
Genzyme Corporation, Framingham, MA 01701.
J Immunol. 1991 Feb 1;146(3):928-35.
Murine/human chimeric antibodies with specificity for the human TCR-alpha/beta have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 were isolated and inserted into mammalian expression vectors containing the human kappa and gamma 1 or gamma 4 C region exons. The chimeric genes were transfected into murine Sp2/O hybridoma cells by electroporation and transfectomas secreting chimeric antibody were isolated. Secretion levels ranged from 1 to 7 pg/cell/24 h. The chimeric antibodies bound specifically to T cells and competed effectively with the parental murine mAb for binding to these sites. The ability to promote antibody-dependent cell-mediated cytolysis was significantly enhanced in the chimeric antibodies as compared with murine BMA 031. C-dependent cytolysis, however, was not detectable with any of the antibodies. Chimeric BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft-vs-host disease, autoimmune diseases and other T cell-related disorders.
通过基因工程制备了对人TCR-α/β具有特异性的鼠/人嵌合抗体。分离出编码鼠单克隆抗体BMA 031的轻链和重链V区外显子，并将其插入含有人类κ链和γ1或γ4恒定区外显子的哺乳动物表达载体中。通过电穿孔将嵌合基因转染到鼠Sp2/O杂交瘤细胞中，并分离出分泌嵌合抗体的转染瘤细胞。分泌水平为1至7 pg/细胞/24小时。嵌合抗体特异性结合T细胞，并能与亲本鼠单克隆抗体有效竞争结合这些位点。与鼠BMA 031相比，嵌合抗体促进抗体依赖性细胞介导的细胞溶解的能力显著增强。然而，任何一种抗体均未检测到补体依赖性细胞溶解。嵌合BMA 031是一种具有临床相关性的基因工程抗体，在移植、移植物抗宿主病、自身免疫性疾病和其他与T细胞相关的疾病中具有潜在用途。
