Although there are many challenges in using nanobodies for treating various complex tumor diseases, including rapid renal clearance and the complex blood-brain barrier environment, nanobodies have shown great potential due to their high antigen affinity, excellent tumor penetration ability, and favorable safety profile. Since the discovery of the variable domain (VHH) of camelid heavy-chain antibodies in 1993, nanobodies have been progressively applied to various cancer therapy platforms, such as antagonistic drugs and targeting agents for effector domains. In recent years, several nanobody-based drugs, including Caplacizumab, KN-035, and Ozoralizumab, have been approved for clinical use.
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