Traunecker A, Lanzavecchia A, Karjalainen K
Basel Institute for Immunology, Switzerland.
EMBO J. 1991 Dec;10(12):3655-9. doi: 10.1002/j.1460-2075.1991.tb04932.x.
The human immunodeficiency virus type 1 (HIV-1) uses cell surface CD4 as a receptor to infect susceptible cells. Therefore, different forms of soluble CD4 (sCD4) molecules have been developed recently for potential therapeutic purposes. Here we describe a novel design of sCD4 molecules which exploit cytotoxic T cells as their effector function. The principle of bispecific antibodies was exploited and further developed to create new bispecific reagents which could retarget cytotoxic T cells of any specificity and thus, induce killing of HIV-1 infected cells. The most advanced molecules, Janusins, contain in one polypeptide chain the first two N-terminal CD4 domains and single chain combining site against the human CD3 complex (FvCD3).
1型人类免疫缺陷病毒（HIV-1）利用细胞表面的CD4作为受体来感染易感细胞。因此，为了潜在的治疗目的，近来已开发出不同形式的可溶性CD4（sCD4）分子。在此，我们描述了一种sCD4分子的新设计，该设计利用细胞毒性T细胞作为其效应功能。双特异性抗体的原理得到利用并进一步发展，以创建新的双特异性试剂，这些试剂可以重新靶向任何特异性的细胞毒性T细胞，从而诱导杀死HIV-1感染的细胞。最先进的分子，即Janusins，在一条多肽链中包含前两个N端CD4结构域以及针对人CD3复合物的单链结合位点（FvCD3）。
