Thoreau Fabien, Chudasama Vijay
Department of Chemistry, University College London 20 Gordon Street London WC1H 0AJ UK
RSC Chem Biol. 2021 Oct 22;3(2):140-169. doi: 10.1039/d1cb00082a. eCollection 2022 Feb 9.
In the past two decades, immunotherapy has established itself as one of the leading strategies for cancer treatment, as illustrated by the exponentially growing number of related clinical trials. This trend was, in part, prompted by the clinical success of both immune checkpoint modulation and immune cell engagement, to restore and/or stimulate the patient's immune system's ability to fight the disease. These strategies were sustained by progress in bispecific antibody production. However, despite the decisive progress made in the treatment of cancer, toxicity and resistance are still observed in some cases. In this review, we initially provide an overview of the monoclonal and bispecific antibodies developed with the objective of restoring immune system functions to treat cancer (cancer immunotherapy), through immune checkpoint modulation, immune cell engagement or a combination of both. Their production, design strategy and impact on the clinical trial landscape are also addressed. In the second part, the concept of multispecific antibody formats, notably MuTICEMs (Multispecific Targeted Immune Cell Engagers & Modulators), as a possible answer to current immunotherapy limitations is investigated. We believe it could be the next step to take for cancer immunotherapy research and expose why bioconjugation chemistry might play a key role in these future developments.
在过去二十年中，免疫疗法已成为癌症治疗的主要策略之一，相关临床试验数量呈指数级增长就说明了这一点。这种趋势部分是由免疫检查点调节和免疫细胞衔接的临床成功所推动的，目的是恢复和/或刺激患者免疫系统对抗疾病的能力。双特异性抗体生产方面的进展支撑了这些策略。然而，尽管在癌症治疗方面取得了决定性进展，但在某些情况下仍观察到毒性和耐药性。在本综述中，我们首先概述了为通过免疫检查点调节、免疫细胞衔接或两者结合来恢复免疫系统功能以治疗癌症（癌症免疫疗法）而开发的单克隆抗体和双特异性抗体。还讨论了它们的生产、设计策略以及对临床试验格局的影响。在第二部分中，研究了多特异性抗体形式的概念，特别是多特异性靶向免疫细胞衔接器和调节剂（MuTICEMs），作为应对当前免疫疗法局限性的一种可能答案。我们认为这可能是癌症免疫疗法研究的下一步，并阐述了生物共轭化学为何可能在这些未来发展中发挥关键作用。
