Nanobodies and their derivatives: pioneering the future of cancer immunotherapy

作者：Haixia Li, Quan Zhou, Nan Cao, Chenghao Hu, Jincheng Wang, Yu He, Shan Jiang, Qi Li, Miao Chen, Gong Li, Ming Luo, Xinzhou Deng, Zhiguo Luo · 发表于：Cell Communication and Signaling · 年份：2025 · DOI：10.1186/s12964-025-02270-4 · 被引用次数：26 · 研究领域：CAR-T cell therapy research、Monoclonal and Polyclonal Antibodies Research、Nanowire Synthesis and Applications

Cancer immunotherapy, which boosts the immune system to recognize and attack malignant cells, has revolutionized traditional cancer treatment paradigms. Approaches such as chimeric antigen receptor T cell (CAR-T) therapy and immune checkpoint inhibitors (ICIs) have demonstrated promising therapeutic outcomes, leading to the approval of numerous immuno-oncology agents by the US Food and Drug Administration (FDA) over the past few decades. Immuno-oncology agents, mainly based on conventional full-length antibodies or their derivatives, are widely used in cancer immunotherapy. However, their large size, unwanted immunogenicity, poor solubility, complex molecular architectures, and limited tumor penetration pose significant challenges that must be addressed. Nanobodies, which are single-domain antibody fragments originating from the variable regions of camelid heavy-chain immunoglobulins, represent the smallest known antigen-binding fragments. In addition to their small size (~ 15 kDa), nanobodies possess a range of advantageous properties, including high stability, strong specificity and affinity for target antigens, low immunogenicity, and cost-effective production. Nonetheless, their short serum half-life and lack of Fc-mediated functions may limit efficacy, which can be addressed by Fc fusion, albumin binding, or multivalent construct design. These properties enable nanobodies to support multifunctional constructs, such as bispecific CARs, nanobody-secreting CARs, dual ICI-co...