Molecular Neurotherapy and Imaging Laboratory, Stem Cell Therapeutics and Imaging Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Molecular Neurotherapy and Imaging Laboratory, Stem Cell Therapeutics and Imaging Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Lancet Oncol. 2015 Nov;16(15):e543-e554. doi: 10.1016/S1470-2045(15)00039-X.
During the past decade, monospecific antibodies targeting cell-surface receptors in different tumour types have achieved substantial success and have been at the forefront of cancer treatment. However, redundant signalling and crosstalk between different pathways within tumour cells and between tumour cells and their microenvironment can limit the efficacy of receptor-targeted monospecific-based therapies. Advances in antibody engineering technologies have enabled strategies that simultaneously target multiple receptors to circumvent the limitations of conventional monospecific therapies and achieve enhanced therapeutic efficacy. In the past 5 years, a range of multifunctional, receptor-targeting, antibody-based molecules have emerged, which allow targeting of multiple surface receptors on tumour cells and endothelial or immune cells in the tumour microenvironment. In this Review, we discuss the rationales and strategies for the use of multifunctional receptor-targeting antibodies, their mechanisms of action, and the promises and challenges they hold as cancer therapeutics. This knowledge provides opportunities to improve current targeted therapy outcomes for patients with cancer.
在过去的十年中，针对不同肿瘤类型的细胞表面受体的单克隆抗体已经取得了实质性的成功，并处于癌症治疗的前沿。然而，肿瘤细胞内不同通路之间以及肿瘤细胞与其微环境之间的冗余信号和串扰会限制受体靶向单克隆治疗的疗效。抗体工程技术的进步使同时靶向多个受体的策略成为可能，从而规避了传统单克隆治疗的局限性，并实现了增强的治疗效果。在过去的 5 年中，出现了一系列多功能、受体靶向的抗体药物，这些药物可靶向肿瘤细胞表面和肿瘤微环境中的内皮细胞或免疫细胞上的多个表面受体。在这篇综述中，我们讨论了使用多功能受体靶向抗体的原理和策略、它们的作用机制，以及它们作为癌症治疗药物的前景和挑战。这些知识为改善癌症患者的现有靶向治疗效果提供了机会。
