Abstract
In recent decades, recombinant antibodies against specific antigens have shown great promise for the therapy of infectious diseases and cancer. Human papillomaviruses (HPVs) are involved in the development of around 5% of all human cancers and HPV16 is the high-risk genotype with the highest prevalence worldwide, playing a dominant role in all HPV-associated cancers. Here, we describe the main biological activities of the HPV16 E6, E7, and E5 oncoproteins, which are involved in the subversion of important regulatory pathways directly associated with all known hallmarks of cancer. We then review the state of art of the recombinant antibodies targeted to HPV oncoproteins developed so far in different formats, and outline their mechanisms of action. We describe the advantages of a possible antibody-based therapy against the HPV-associated lesions and discuss the critical issue of delivery to tumour cells, which must be addressed in order to achieve the desired translation of the antibodies from the laboratory to the clinic.
Highlights
In the last decades, because of the huge advances of recombinant DNA technology, recombinant antibodies have found increasing applications in the therapy of many diseases, whether of genetic, infectious, or tumour origin
To the best of our knowledge, the different formats of recombinant antibodies against the Human papillomaviruses (HPVs) oncoproteins of Human Papillomaviruses characterized to date or currently under study and discuss whether and why they show promise for the treatment of pre-neoplastic and neoplastic lesions caused by these viruses
Since its X-ray structure in complex with E6-associated protein (E6AP), the ubiquitin ligase involved in p53 polyubiquitination, and p53 has been resolved, the possibility of inhibiting this complex has been increasingly investigated through several methods among which those based on specific recombinant antibodies appear promising
Summary
Because of the huge advances of recombinant DNA technology, recombinant antibodies have found increasing applications in the therapy of many diseases, whether of genetic, infectious, or tumour origin. The use of display technologies allows in vitro selection from non-animal-derived recombinant (naïve or synthetic) repertoires (libraries) of peptides and antibody fragments in different formats such as Fab fragments (Fabs), scFvs, and Nbs. Different platforms are available such as phage display, yeast display, ribosome display, bacterial display, mammalian cell surface display, mRNA display, and DNA display. CDRs with specific binding activities can be isolated and grafted onto different scaffolds suitable for the purposes of interest Both scFv and Fab fragments can be engineered into stable oligomers. Thanks to the small size, VHHs can penetrate tissues and access cryptic epitopes [11,12] They are more soluble and capable of efficient folding with respect to conventional mAbs, which renders them suitable for high-yield production in E. coli and even for delivery to or expression in infected cells as intrabodies. VHHs targeting haematological, oncological, infectious, inflammatory/auto-immune, bone and neurological diseases are already being evaluated in clinical trials, while the humanized VHH Caplacizumab (CabliviTM) was recently approved in Europe and USA for the treatment of acquired thrombotic thrombocytopenic purpura [14,15,16]
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