De Jonge J, Heirman C, De Veerman M, Van Meirvenne S, Demanet C, Brissinck J, Thielemens K
Laboratory of Physiology, Medical School, Vrije Universiteit Brussel, (VUB), Belgium.
Cancer Immunol Immunother. 1997 Nov-Dec;45(3-4):162-5. doi: 10.1007/s002620050423.
This report summarizes our experimental data concerning the use of bispecific antibodies (bsAb) for the treatment of the murine BCL1 B cell lymphoma model. Initially we used a hybrid-hybridoma-derived bsAb with specificity for the TcR/CD3 complex on T cells and the idiotype of the membrane-bound IgM on the tumor cells. The bsAb used as a single agent could cure animals with a low tumor load (resembling minimal residual disease). However, in experiments aimed at increasing the therapeutic effect in animals with a higher tumor burden, we could demonstrate the importance of additional T-cell-costimulatory signals and the careful timing of the bsAb administration. Recently we have generated a bispecific single-chain Fv (bsscFv) fusion protein with the same dual specificity as the hybrid-hybridoma-derived bsAb. Immunotherapy with this smaller molecule also resulted in tumor elimination in BCL1-bearing mice. A second bsscFv (alpha-CD19 x alpha-CD3) with a broader applicability is now being characterized and tested in vivo.
本报告总结了我们关于使用双特异性抗体（bsAb）治疗小鼠BCL1 B细胞淋巴瘤模型的实验数据。最初，我们使用了一种源自杂交杂交瘤的bsAb，它对T细胞上的TcR/CD3复合物以及肿瘤细胞上膜结合IgM的独特型具有特异性。作为单一药物使用的bsAb可以治愈肿瘤负荷低的动物（类似于微小残留病）。然而，在旨在提高对肿瘤负荷较高动物的治疗效果的实验中，我们能够证明额外的T细胞共刺激信号以及bsAb给药的精确时机的重要性。最近，我们生成了一种双特异性单链Fv（bsscFv）融合蛋白，其具有与源自杂交杂交瘤的bsAb相同的双重特异性。用这种较小的分子进行免疫治疗也导致了携带BCL1的小鼠体内肿瘤的消除。现在正在对另一种具有更广泛适用性的bsscFv（α-CD19×α-CD3）进行体内表征和测试。
