Middelburg Jim, Kemper Kristel, Engelberts Patrick, Labrijn Aran F, Schuurman Janine, van Hall Thorbald
Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Genmab, 3584 CT Utrecht, The Netherlands.
Cancers (Basel). 2021 Jan 14;13(2):287. doi: 10.3390/cancers13020287.
Immunotherapy of cancer with CD3-bispecific antibodies is an approved therapeutic option for some hematological malignancies and is under clinical investigation for solid cancers. However, the treatment of solid tumors faces more pronounced hurdles, such as increased on-target off-tumor toxicities, sparse T-cell infiltration and impaired T-cell quality due to the presence of an immunosuppressive tumor microenvironment, which affect the safety and limit efficacy of CD3-bispecific antibody therapy. In this review, we provide a brief status update of the CD3-bispecific antibody therapy field and identify intrinsic hurdles in solid cancers. Furthermore, we describe potential combinatorial approaches to overcome these challenges in order to generate selective and more effective responses.
用CD3双特异性抗体进行癌症免疫治疗是一些血液系统恶性肿瘤的已批准治疗选择，目前正在对实体癌进行临床研究。然而，实体瘤的治疗面临着更明显的障碍，如脱靶肿瘤毒性增加、T细胞浸润稀疏以及由于免疫抑制性肿瘤微环境的存在导致T细胞质量受损，这些都会影响CD3双特异性抗体治疗的安全性并限制其疗效。在本综述中，我们简要介绍了CD3双特异性抗体治疗领域的最新情况，并确定了实体癌中的内在障碍。此外，我们描述了潜在的联合方法来克服这些挑战，以产生选择性更强、更有效的反应。
