Scope of nanobodies in hepatopancreatobiliary oncology

Hepatopancreatobiliary (HPB) cancers remain among the most aggressive malignancies. Nanobodies are single-domain antibodies derived from camelid heavy-chain-only immunoglobulins. They offer distinct advantages, including small size, stability, and high antigen affinity, enabling superior tumor penetration and specificity. Emerging nanobody-drug conjugates, multispecific constructs, radiolabeled probes, and nanobody-functionalized nanoparticle platforms have shown promising preclinical outcomes in HPB cancers. Thus, this review summarizes recent advances in nanobody engineering, focusing on approaches to improve pharmacokinetics, enhance tumor penetration, enhance therapeutic performance, and modulate the tumor microenvironment. This article also addresses key challenges in the clinical translation and large-scale production of nanobodies for precise diagnosis and treatment applications in HPB oncology.