Weidle Ulrich H, Kontermann Roland E, Brinkmann Ulrich
Roche Pharmaceuticals Research and Early Development (pRED), Discovery Oncology (UHW) and Large Molecule Research (UB), Roche Innovation Center Penzberg, Germany.
Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
Semin Oncol. 2014 Oct;41(5):653-60. doi: 10.1053/j.seminoncol.2014.08.004. Epub 2014 Aug 12.
Bi- and multispecific antibody derivatives (bsAbs) can be considered as the next generation of targeted biologics for cancer therapy. The general concept of bsAbs is a physical connection of recombinant antibody-derived entities with at least two binding specificities. This generates bsAbs that bind at least two antigens or epitopes, thus altering their binding functionalities and specificities in comparison to "normal" antibodies. Most bsAbs are produced as recombinant proteins, either as large IgG-like proteins that contain Fc regions, or as smaller entities with multiple antigen-binding regions but without Fc. Application of bsAbs in experimental cancer therapy currently includes molecules that bind different cell surface proteins to achieve more complete blockage of proliferative or angiogenesis-associated pathways. This approach of blocking more than one pathway component, or to simultaneously hit complementing pathways, also may limit potential escape mechanisms of cancer cells. BsAbs also are applied in the clinic as vehicles to deliver immune effector cells and/or cytokines to tumors.
双特异性和多特异性抗体衍生物（双特异性抗体）可被视为癌症治疗的下一代靶向生物制剂。双特异性抗体的总体概念是具有至少两种结合特异性的重组抗体衍生实体的物理连接。这产生了能结合至少两种抗原或表位的双特异性抗体，因此与“正常”抗体相比，其结合功能和特异性发生了改变。大多数双特异性抗体作为重组蛋白产生，要么是含有Fc区域的大的IgG样蛋白，要么是具有多个抗原结合区域但没有Fc的较小实体。双特异性抗体在实验性癌症治疗中的应用目前包括结合不同细胞表面蛋白以更完全地阻断增殖或血管生成相关途径的分子。这种阻断多个途径成分或同时作用于互补途径的方法，也可能限制癌细胞的潜在逃逸机制。双特异性抗体在临床上也用作将免疫效应细胞和/或细胞因子递送至肿瘤的载体。
