Department of Medicine, Division of Hematology/Oncology, University of Virginia Cancer Center, Charlottesville, VA, USA.
Department of Medicine, Division of Hematology/Oncology, University of Virginia Cancer Center, Charlottesville, VA, USA.
Blood Rev. 2018 Jul;32(4):339-347. doi: 10.1016/j.blre.2018.02.004. Epub 2018 Feb 20.
Monoclonal antibody-based targeted therapy has greatly improved treatment options for patients. However, long-term efficacy of such antibodies is limited by resistance mechanisms. New insights into the mechanisms by which tumors evade immune control have driven innovative therapeutic strategies to eliminate cancer by re-directing immune cells to tumors. Advances in protein engineering technology have generated multiple bispecific antibody (BsAb) formats capable of targeting multiple antigens as a single agent. Approval of two BsAb and three check point blocking mAbs represent a paradigm shift in the use of antibody constructs. Since BsAbs can directly target immune cells to tumors, drug resistance and severe adverse effects are much reduced. The wave of next generation "bispecific or multispecific antibodies" has advanced multiple candidates into ongoing clinical trials. In this review, we focus on preclinical and clinical studies in hematological malignancies as well as discuss reasons for the limited success of BsAbs against solid tumors.
基于单克隆抗体的靶向治疗极大地改善了患者的治疗选择。然而，此类抗体的长期疗效受到耐药机制的限制。肿瘤逃避免疫控制机制的新见解促使人们采用创新的治疗策略，通过将免疫细胞重新导向肿瘤来消除癌症。蛋白质工程技术的进步产生了多种双特异性抗体 (BsAb) 形式，可作为单一药物靶向多种抗原。两种 BsAb 和三种检查点阻断 mAb 的批准代表了抗体构建物使用的范式转变。由于 BsAb 可直接将免疫细胞靶向肿瘤，因此耐药性和严重不良反应大大减少。下一代“双特异性或多特异性抗体”浪潮使多个候选药物推进到正在进行的临床试验中。在这篇综述中，我们重点关注血液系统恶性肿瘤的临床前和临床研究，并讨论了 BsAb 针对实体瘤疗效有限的原因。
