Bispecific molecules redirecting the cytotoxicity of T-cells are a growing class of therapeutics with numerous molecules being tested in clinical trials. However, it has been a long way since the proof of concept studies in the mid 1980's. In the process we have learnt about the impact of different variables related to the bispecific molecule and the target antigen on the potency of this type of drugs. This work reviews the insights gained and how that knowledge has been used to design more potent bispecific T-cell engagers. The more recent advancement of antibodies with this modality into safety studies in non-human primates and as well as in clinical studies has revealed potential toxicity liabilities for the mode of action. Modifications in existing antibody formats and new experimental molecules designed to mitigate these problems are discussed.

中文翻译：

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双特异性 T 细胞接合器：了解影响体外效力和肿瘤选择性的变量及其调节，以提高其功效和安全性

重定向 T 细胞细胞毒性的双特异性分子是一类不断增长的治疗方法，其中许多分子正在临床试验中进行测试。然而，自 1980 年代中期进行概念验证研究以来，已经有很长的路要走。在此过程中，我们了解了与双特异性分子和目标抗原相关的不同变量对此类药物效力的影响。这项工作回顾了获得的见解以及这些知识如何用于设计更有效的双特异性 T 细胞接合器。在非人类灵长类动物的安全性研究和临床研究中，采用这种方式的抗体的最新进展揭示了该作用方式的潜在毒性。