Promising Diagnostic and Therapeutic Approaches Based on VHHs for Cancer Management

Simple Summary With around 15 kD molecular weight, VHHs are considered the smallest antigen-binding fragments. Based on their unique properties, VHHs have broad application prospects such as bio-sensing, molecular imaging, drug delivery, disease treatments, and diagnosis. In this review, we discuss VHH applications for cancer treatments and diagnosis. Meanwhile, an overview of VHH-based agents in clinical trials is provided.Abstract The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined. The preclinical studies illustrating the diagnostic and therapeutic efficacy of distinct VHHs in diverse formats against solid cancers are summarized, and an overview of the clinical trials assessing VHH-based agents in oncology is provided. These investigations demonstrate the enormous potential of VHHs for medical research and healthcare.