Anti-HPV18 E7 monoclonal antibody, clone 829-26

The main scourge of cervical intraepithelial neoplasia and cervical cancer is human papilloma virus (HPV) (both HPV 16 and 18) found here. HPV virus is an envelopeless, double-stranded DNA virus whose genome contains a double promoter that encodes two separate viral proteins: early proteins (E1, E2, E4, E5, E6, E7) and late proteins (L1, L2). They have different pathways and processes to encourage cancer to occur in the wake of HPV. When you get high-risk HPV, the bulk of the virus is identified and cleared by your innate and adaptive immune system; very few get away and reinfect the body, further degrading it.

Risk HPV early proteins disrupt the cGAS-STING-TBK1 signaling axis and inhibit the host immune system from seeing HPV DNA and suppressing the immune response. HPV18 E7 can activate SUV39H1, and thus block the cGAS-STING pathway. Additionally, HPV18 E7 can suppress this pathway through other epigenetic mechanisms. E7 binds to STING directly, via a pRb-binding motif, preventing the cGAS-STING pathway. HPV early proteins can turn down the Toll-like receptor (TLR) gene expression and impede NFκB dimer formation and function by suppressing the activation of the NFκB pathway. In healthy humans, TLR9 is capable of detecting DNA, and thus starts signalling cascades that regulate the production of pro-inflammatory cytokines and type I interferons (among other molecules required for starting immune responses) to activate and stimulate immune response. High-risk HPV E6 and E7 can bind to P300/CBP-associated factors, thereby reducing NF-κB activity. Furthermore, HPV E7 can promote immune evasion by inhibiting pyroptosis through facilitating the degradation of IFI16 inflammasomes mediated by TRIM21 and K33-linked ubiquitination.

Figure 1. Schematic representation of HPV E6/E7-mediated cellular transformation
(Source: Vats A, et al. 2021)

In adaptive immunity, early proteins evade the immune system by inhibiting antigen-presenting cells from presenting antigens to T cells, while also suppressing T cell recognition of antigens and their own activation. HPV18 E7 can inhibit the bidirectional promoter associated with the transport proteins TAP1 and LMP2, mediating the transcriptional downregulation of TAP1 and LMP2 genes, thereby suppressing antigen processing and transport.

Anti-Human papillomavirus 18 E7 monoclonal antibody
Anti-Human papillomavirus type 18 E7 monoclonal antibody