Integrated in silico-in vitro identification of high-affinity TCR-Like antibodies targeting HPV18 E6/E7 for cervical...

The aim of this study was to evaluate the diagnostic potential of human papillomavirus type 18 (HPV18) E6/E7-specific T cell receptor (TCR)-like antibodies for the early detection of HPV-associated cervical cancer. An integrated in silico and in vitro approach was employed, in which three fully human TCR-like antibodies (H11\Ab, E5\Ab, and G8\Ab) were analysed by molecular docking to assess antibody-peptide-major histocompatibility complex (P-MHC) class I HLA-A24:02 interactions, followed by experimental validation using SiHa and C33A cervical cancer cell lines. Docking analyses demonstrated stable, high-affinity interactions between the antibodies and their corresponding peptide-MHC complexes, consistent with experimental observations. In vitro assays confirmed strong binding specificity and functional activity in HPV18-positive cells, with no detectable reactivity in HPV-negative controls. These findings demonstrate that TCR-like antibodies targeting HPV18 E6/E7 peptide-MHC complexes enable highly specific detection of HPV-associated cervical cancer and support their potential application as early diagnostic biomarkers.