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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
A TCR mimic monoclonal antibody for the HPV-16 E7-epitope p11-19/HLA-A*02:01 complex
Tao Dao1, Sungsoo Mun1, Tatyana Korontsvit1
1Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Abstract:
More effective treatments are needed for human papilloma virus (HPV)-induced cancers despite HPV virus vaccination. The oncogenic HPV protein targets are currently undruggable and intracellular and therefore there are no antibodies to these targets. Here we report the discovery of TCR mimic monoclonal antibodies (TCRm mAb) specific for the HPV E7 protein p11-19, YMLDLQPET, when presented on the cell surface in the context of HLA-A*02:01 by use of human phage display libraries. One of the mAbs, 3F8, was able to specifically mediate T cell- redirected cytotoxicity, in a bispecific T cell engager (BiTE) form. While further studies are required to assess the therapeutic potential of this approach, the study provided the proof of concept that TCRm mAb could be a therapeutic strategy for HPV-induced human cancers.
Insights
New TCR mimic monoclonal antibodies (TCRm mAb) show promise for treating human papilloma virus (HPV)-induced cancers. This approach targets previously undruggable HPV proteins, offering a potential new therapeutic strategy.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Despite HPV vaccination, effective treatments for HPV-induced cancers remain limited.
- Oncogenic HPV proteins are intracellular and undruggable, lacking antibody targets.
Purpose of the Study:
- To discover novel therapeutic strategies for HPV-induced cancers.
- To develop antibodies targeting intracellular HPV oncoproteins.
Main Methods:
- Utilized human phage display libraries to identify TCR mimic monoclonal antibodies (TCRm mAb).
- Screened for antibodies specific to the HPV E7 protein peptide p11-19 (YMLDLQPET) in the context of HLA-A*02:01.
Main Results:
- Discovered TCRm mAbs that specifically recognize the HPV E7 peptide presented by HLA-A*02:01.
- One mAb, 3F8, demonstrated the ability to mediate T cell-redirected cytotoxicity in a bispecific T cell engager (BiTE) format.
Conclusions:
- TCRm mAbs represent a viable therapeutic strategy for HPV-induced cancers.
- This study provides proof of concept for using TCRm mAbs against previously undruggable intracellular targets.
