Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy.
Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy.
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DOI：
10.1158/1078-0432.ccr-20-3770
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发表时间：
2021-10-15
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免疫肿瘤学领域的最新进展极大地改变了对晚期恶性肿瘤的治疗策略。随着T细胞重定向抗体blinatumomab的监管批准，基于双特异性抗体的免疫疗法在临床前和临床研究中获得了势头。在这篇综述中，我们重点介绍了双特异性抗体与免疫细胞相互作用的新的新的作用机制，这些双特异性抗体至少有一只手臂，通过将效应细胞重新定向和/或重新激活到肿瘤细胞来调节免疫系统的活性。这些分子，在这里被称为双特异性免疫调节抗体，具有改善临床疗效和安全性的潜力，并被视为癌症免疫治疗的第二波。目前，有50多种双特异性抗体正在临床开发中，用于一系列适应症，具有良好的治疗活性迹象。我们还讨论了两种体内分泌、直接基因输送和体外基因修饰细胞输注的方法，这可能成为下一代双特异性免疫调节抗体的临床应用工具。
The recent advances in the field of immuno-oncology have dramatically changed the therapeutic strategy against advanced malignancies. Bispecific antibody-based immunotherapies have gained momentum in preclinical and clinical investigations following the regulatory approval of the T cell–redirecting antibody blinatumomab. In this review, we focus on emerging and novel mechanisms of action of bispecific antibodies interacting with immune cells with at least one of their arms to regulate the activity of the immune system by redirecting and/or reactivating effector cells toward tumor cells. These molecules, here referred to as bispecific immunomodulatory antibodies, have the potential to improve clinical efficacy and safety profile and are envisioned as a second wave of cancer immunotherapies. Currently, there are more than 50 bispecific antibodies under clinical development for a range of indications, with promising signs of therapeutic activity. We also discuss two approaches for in vivo secretion, direct gene delivery, and infusion of ex vivo gene-modified cells, which may become instrumental for the clinical application of next-generation bispecific immunomodulatory antibodies.