Nanobodies Open New Avenues in Cancer Treatment: From Molecular Engineering to Therapeutic Platforms.

Nanobody technology is a promising approach in cancer research and treatment. Monoclonal antibodies have long been central to targeted therapies; however, their large size, complex production, and limited tissue penetration restrict their clinical performance. Nanobodies, derived from camelid heavy-chain antibodies, possess unique properties, including small size (~15 kDa), high stability, and the ability to access otherwise inaccessible epitopes. At the molecular and cellular levels, these characteristics arise from a defined structure-function relationship that governs antigen binding, receptor modulation, and downstream signaling. Beyond affinity, nanobody function is influenced by binding kinetics and intracellular trafficking. Their ease of production in bacterial systems further enhances cost-effectiveness compared to conventional antibodies. Nanobody-based strategies have evolved from diagnostic and imaging tools to multifunctional therapeutic platforms, including nanobody-drug conjugates, bispecific and multispecific engagers, immune checkpoint modulators, and engineered cell-based therapies such as CAR-T systems. Preclinical studies have demonstrated improved tumor targeting, enhanced immune activation, and reduced off-target effects. Emerging clinical evidence, including approved nanobody therapeutics and ongoing trials, supports their safety, feasibility, and translational potential in cancer patients. Together, these findings highlight nanobodies as versatile platforms capable of overcoming key limitations of conventional therapies and facilitating clinical translation in precision oncology.