Pfizer BioMedicine Design, Pfizer Inc, San Diego, CA, USA.
Pfizer BioMedicine Design, Pfizer Inc, Cambridge, MA, USA.
Expert Opin Biol Ther. 2022 Aug;22(8):965-982. doi: 10.1080/14712598.2022.2072209. Epub 2022 May 8.
Following the approval of the T cell engaging bispecific antibody blinatumomab, immune cell retargeting with bispecific or multispecific antibodies has emerged as a promising cancer immunotherapy strategy, offering alternative mechanisms compared to immune checkpoint blockade. As we gain more understanding of the complex tumor microenvironment, rules and design principles have started to take shape on how to best harness the immune system to achieve optimal anti-tumor activities.
In the present review, we aim to summarize the most recent advances and challenges in using bispecific antibodies for immune cell retargeting and to provide insights into various aspects of antibody engineering. Discussed herein are studies that highlight the importance of considering antibody engineering parameters, such as binding epitope, affinity, valency, and geometry to maximize the potency and mitigate the toxicity of T cell engagers. Beyond T cell engaging bispecifics, other bispecifics designed to recruit the innate immune system are also covered.
Diverse and innovative molecular designs of bispecific/multispecific antibodies have the potential to enhance the efficacy and safety of immune cell retargeting for the treatment of cancer. Whether or not clinical data support these different hypotheses, especially in solid tumor settings, remains to be seen.
在 T 细胞衔接双特异性抗体blinatumomab 获得批准后，免疫细胞的双特异性或多特异性抗体重定向作为一种很有前途的癌症免疫治疗策略已经出现，与免疫检查点阻断相比，它提供了替代机制。随着我们对复杂肿瘤微环境的了解不断加深，如何利用免疫系统来实现最佳抗肿瘤活性的规则和设计原则开始形成。
在本综述中，我们旨在总结使用双特异性抗体进行免疫细胞重定向的最新进展和挑战，并深入了解抗体工程的各个方面。本文讨论的研究强调了考虑抗体工程参数（如结合表位、亲和力、价态和几何形状）的重要性，以最大限度地提高 T 细胞衔接物的效力并减轻其毒性。除了 T 细胞衔接双特异性抗体，还涵盖了其他旨在招募先天免疫系统的双特异性抗体。
双特异性/多特异性抗体的多样化和创新分子设计有可能提高免疫细胞重定向治疗癌症的疗效和安全性。无论临床数据是否支持这些不同的假设，尤其是在实体瘤环境中，仍有待观察。
