Staerz U D, Kanagawa O, Bevan M J
Nature. 1985;314(6012):628-31. doi: 10.1038/314628a0.
It would be advantageous in the case of certain diseases to be able to focus a strong T-cell response at a chosen target, for example, in treating cancer or infections that have escaped the normal host response. At present, it seems inconceivable that we could use antigen-specific lines or clones of effector T cells for this purpose because of complications due to the major histocompatibility restriction of T-cell specificity and the problem of rejection of transplanted effector cells. Here we describe a novel technology which combines the power of T lymphocytes in eliminating unwanted cells and causing beneficial inflammatory reactions with the great advantages of monoclonal antibodies (their specificity and availability). We show that heteroconjugates of monoclonal antibodies (referred to hereafter as hybrid antibodies), in which one of the component binding sites is anti-T-cell receptor and the other component binding site is directed against any chosen target antigen, can focus T cells to act at the targeted site. Monoclonal antibodies directed against the T-cell receptor, such as the anti-allotype used here, are mitogenic for resting T cells and can be used to induce effector T cells carrying the T-cell receptor determinant which can then be directed against the target by a hybrid antibody.
对于某些疾病而言，若能将强大的T细胞反应聚焦于选定的靶点将是有益的，例如在治疗癌症或逃避正常宿主反应的感染时。目前，由于T细胞特异性的主要组织相容性限制所带来的并发症以及移植效应细胞的排斥问题，我们似乎无法为此目的使用抗原特异性的效应T细胞系或克隆。在此，我们描述了一种新技术，该技术将T淋巴细胞在消除不需要的细胞以及引发有益炎症反应方面的能力与单克隆抗体的巨大优势（其特异性和可得性）相结合。我们表明，单克隆抗体的异源缀合物（以下简称杂交抗体），其中一个组分结合位点是抗T细胞受体，另一个组分结合位点针对任何选定的靶抗原，能够使T细胞聚焦于靶点发挥作用。针对T细胞受体的单克隆抗体，比如此处使用的抗同种异型抗体，对静止T细胞具有促有丝分裂作用，可用于诱导携带该T细胞受体决定簇的效应T细胞，然后通过杂交抗体将其导向靶标。
