Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb–drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy.

中文翻译：

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单域抗体作为实体瘤治疗药物

单域抗体 (sdAb) 最初在骆驼科动物或鲨鱼中发现，通常称为纳米抗体或 VNAR，现已成为传统治疗抗体的有前途的替代品。这些 sdAb 具有许多优越的理化和药理学特性，包括尺寸小、溶解性和热稳定性好、更容易接近的表位以及较强的组织渗透性。然而，与 sdAb 动物来源相关的固有挑战限制了其临床应用。近年来，已经开发出各种创新的人源化技术，包括互补决定区（CDR）移植或全人源化抗体的完整工程，以减轻潜在的免疫原性问题并增强其相容性。这篇综述对 sdAb 进行了全面的探索，强调了它们的独特特征和人源化方法的进展。此外，我们还概述了基于 sdAb 的药物和治疗策略开发的最新进展及其在实体瘤治疗中的潜力，例如 sdAb-药物缀合物、多特异性 sdAb、基于 sdAb 的递送系统和基于 sdAb 的细胞疗法。