The Potential Applicability of Single-Domain Antibodies (VHH): From Checkpoint Blockade to Infectious Disease Therapy

Monoclonal antibodies (mAbs) have demonstrated promising clinical efficacy in various therapeutic fields over the past decades. However, their size has emerged as the most restricting factor limiting their application in antibody-drug conjugate platforms or antibody-redirected delivery systems. This limitation was mainly due to the inability of these platforms to penetrate the tumor site and reach their intended destination. Single-domain antibodies, also known as VHHs or nanobodies®, are known as promising alternatives capable of addressing the drawbacks of conventional full-sized antibodies. Alongside a great level of affinity and selectivity towards their target, the small size of nanobodies, which is about 15 kDa, their capability for tissue penetrance, the significant level of stability, their simple and cost-friendly manufacturing process, and fleeting half-life in the circulation system, are all among the reasons that have made them suitable candidates for the development of various types of therapies. In this review, we briefly discuss the application of nanobodies in checkpoint blockade therapy and nanobody-drug conjugate platforms. We also discuss nanobody-assisted redirection of various types of delivery systems carrying different types of cargoes. In the last section, we underline the promising and effective application of nanobodies in the fight against infectious diseases.