Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
In Vivo Cellular and Molecular Imaging Laboratory, Department of Medical Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
Int Rev Cell Mol Biol. 2022;369:143-199. doi: 10.1016/bs.ircmb.2022.03.010. Epub 2022 May 18.
Cancer is a heterogeneous disease, requiring treatment tailored to the unique phenotype of the patient's tumor. Monoclonal antibodies (mAbs) and variants thereof have enabled targeted therapies to selectively target cancer cells. Cancer cell-specific mAbs have been used for image-guided surgery and targeted delivery of radionuclides or toxic agents, improving classical treatment strategies. Cancer cell-specific mAbs can further inhibit tumor cell growth or can stimulate immune-mediated destruction of cancer cells, a feature that has also been achieved through mAb-mediated manipulation of immune cells and pathways. Drawbacks of mAbs and their variants, together with the discovery of camelid heavy chain-only antibodies and the many advantageous features of their variable domains, referred to as VHs, single domain antibodies or nanobodies (Nbs), resulted in the exploration of Nbs as an alternative targeting moiety. We therefore review the state-of-the-art as well as novel exploitation strategies of Nbs for targeted cancer therapy.
癌症是一种异质性疾病，需要根据患者肿瘤的独特表型进行个体化治疗。单克隆抗体（mAbs）及其变体使靶向治疗能够选择性地针对癌细胞。针对癌细胞的 mAbs 已用于图像引导手术和放射性核素或毒性药物的靶向递送，从而改善了经典的治疗策略。针对癌细胞的 mAbs 可以进一步抑制肿瘤细胞的生长，或者可以刺激免疫介导的癌细胞破坏，这一特性也可以通过 mAb 介导的免疫细胞和途径的操纵来实现。mAbs 及其变体的缺点，以及骆驼重链仅抗体的发现及其可变结构域（称为 VH）的许多有利特征，被称为单域抗体或纳米抗体（Nbs），促使人们探索 Nbs 作为替代靶向部分。因此，我们综述了 Nbs 作为靶向癌症治疗的新型靶向部分的最新进展和新的开发策略。
