Targeting the Human Papillomavirus 16 E6 Oncoprotein with Antibodies

Abstract

The human papillomavirus (HPV) 16 genome encodes two oncoproteins, E6 and E7, which are essential for viral carcinogenesis. While E7 promotes cell proliferation, E6 abolishes the resulting p53-dependent apoptotic response. Due to this specific function, E6 is considered a suitable target for the development of a variety of therapeutic agents such as antibodies. Here, we review anti-E6 antibodies/antibody fragments generated by us and others, as well as present our latest results with Camelidae-derived single-domain antibodies (sdAbs). We had previously isolated a pool of anti-E6 sdAbs to identify E6 binders with the potential to be used clinically and in research. While our previous work has focused on recombinant E6 proteins, here we evaluated these sdAbs binding capacity to the endogenous E6 protein using co-immunoprecipitation and immunofluorescence. We obtained reproducible results in these applications with two sdAbs, filling a gap in HPV research. Despite their apparent E6 binding ability, these sdAbs do not raise p53 levels or induce apoptosis. Thus, while these reagents are valuable diagnostic and detection tools, identifying their therapeutic potential will require further development and testing.