The Small and Powerful Nanobodies (Nbs) Originating from Peculiar Animals used for Therapy of Cancers

A conventional antibody is structurally featured with two heavy chains and two light ones. However, a simpler version termed as heavy-chain antibody (HCAb), also naturally exists in the serum of peculiar animal such as camels and llamas. HCAb contains a single heavy chain with one variable domain (VHH domain) and two constant domains (CH2 and CH3 domain). Interestingly, the fragment corresponding to single variable domain in HCAb can exist stably and work independently (nanobody, Nb), something like an abbreviated HCAb. Its smaller molecular weight confers Nbs unique and prominent merits including low possibility of eliciting undesirable immune response, strong tissue penetrability, high stability and ease of production. In this review, after discussing the features of Nb, we systematically reviewed the most recent advances in the wide applications of Nbs in the everlasting war against cancer. More emphasis is put on their applications as cancer therapeutics agents (ligand blocker, receptor antagonist) and as components of cancer therapeutic bioconjugates (with exotoxin, liposome, T-lymphocyte, or enzyme)