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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Bassam Ali Sachit,
  • Sylvia Dass,
  • Rehasri Selva Rajan,
  • Gee Jun Tye,
  • Venugopal Balakrishnan

摘要

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.