Demanet C, Brissinck J, Van Mechelen M, Leo O, Thielemans K
Unit of Hematology-Immunology, Medical School, Vrije Universiteit Brussel (VUB), Belgium.
J Immunol. 1991 Aug 1;147(3):1091-7.
It has previously been reported that T lymphocytes can be targeted by using bispecific antibodies consisting of anti-target antibody and anti-CD3. In the present study, a bispecific mAb was developed by somatic hybridization of mouse hybridomas, one producing a mAb against the Id determinant of the mouse B cell lymphoma 38C13 and the other a mAb against a polymorphic determinant on murine CD3. The bispecific antibody, anti-38C13 x anti-CD3, is bi-isotypic (IgG1 x IgG2a) and was purified by ion exchange and affinity chromatography. The dual specificity of the hybrid hybridoma-produced mAb could be demonstrated by flow cytometry, the induction of T cell proliferation, the induction of IL-2 secretion by polyclonal T cells, and redirected lysis of the relevant target cells. The hybrid (bi-isotypic) Fc part of the bispecific antibodies was nonfunctional in FcR-dependent redirected lysis. In vivo studies demonstrate that this bispecific mAb could efficiently target T cells towards the tumor cells, resulting in long term survival and cure of the lymphoma.
此前有报道称，可通过使用由抗靶标抗体和抗CD3组成的双特异性抗体来靶向T淋巴细胞。在本研究中，通过小鼠杂交瘤的体细胞杂交开发了一种双特异性单克隆抗体，其中一个杂交瘤产生针对小鼠B细胞淋巴瘤38C13的独特型决定簇的单克隆抗体，另一个产生针对小鼠CD3上多态性决定簇的单克隆抗体。双特异性抗体抗-38C13×抗-CD3是双同型的（IgG1×IgG2a），并通过离子交换和亲和色谱法进行纯化。杂交杂交瘤产生的单克隆抗体的双重特异性可通过流式细胞术、T细胞增殖的诱导、多克隆T细胞IL-2分泌的诱导以及相关靶细胞的重定向裂解来证明。双特异性抗体的杂交（双同型）Fc部分在FcR依赖性重定向裂解中无功能。体内研究表明，这种双特异性单克隆抗体可有效地将T细胞靶向肿瘤细胞，从而导致淋巴瘤的长期存活和治愈。
