Materials and methods relating to immunogenic epitopes from human papilloma virus
Inventors
Krishna, Sri • Posner, Marshall • SIKORA, Andrew • Anderson, Karen
Assignees
Baylor College of Medicine • Icahn School of Medicine at Mount Sinai • Arizona State University Downtown Phoenix campus
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12551546-B2
Publication Date
2026-02-17
Expiration Date
Abstract
Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.
Core Innovation
The invention discloses novel HPV16 E2/E6/E7 CD8+ cytotoxic T lymphocyte (CTL) epitopes restricted by common HLA class I alleles. These epitopes comprise amino acid sequences selected from VVEGQVDYY, HPAATHTKAV, QVILCPTSV, NPCHTTKLL, GIRTYFVQF, or YYVHEGIRTY, and the CTL epitope is no more than 10 amino acids in length. The epitopes are presented in the context of HPV16+ head and neck squamous cell carcinoma (HNSCC) and are associated with CD8+ CTL recognition.
The invention addresses detection and quantification of epitope-specific T cells for diagnosis and immunotherapy of HPV16-associated disease. It provides immunogenic compositions that can include the disclosed immunogenic epitopes and describes generating and/or quantifying epitope-specific T cells using an MHC class I peptide tetramer assay that measures T cells capable of binding at least one synthetic polypeptide comprising a CTL epitope from an E2, E6, or E7 HPV16 antigen.
The invention also discloses a combined strategy involving immune checkpoint blockade. It describes immune checkpoint mechanisms associated with HPV16 antigen-driven T-cell exhaustion/dysfunction and identifies IDO-1 as an immune checkpoint target linked to HPV16 signaling, especially E7, with synergy with PD-1 inhibition to enhance CTL-mediated cytotoxicity and CTL response patterns associated with HLA allele frequency and patient serology.
Claims Coverage
The provided materials include 1 independent claim. The claims cover detection and quantification of CTL epitope-binding T cells using an MHC tetramer assay, with epitope sequence options limited to CTL epitopes of no more than 10 amino acids drawn from specific HPV16 antigen sources.
MHC tetramer assay for HPV16 CTL epitope-binding T cells
A method of detecting an HPV-16-associated disease comprising obtaining a biological sample comprising T cells, performing an MHC tetramer assay, and detecting or quantifying T cells capable of binding at least one synthetic polypeptide comprising a CTL epitope from an E2 HPV16 antigen, wherein the CTL epitope is no more than 10 amino acids in length and comprises an amino acid sequence selected from VVEGQVDYY, HPAATHTKAV, QVILCPTSV, NPCHTTKLL, GIRTYFVQF, or YYVHEGIRTY; wherein the detection or quantification indicates the presence of an HPV-16-associated disease.
Extending epitope sources to HPV16 E6 and/or E7 CTL epitopes
The method further detects or quantifies T cells capable of binding at least one synthetic polypeptide comprising a CTL epitope from an HPV16 E6 antigen and/or an HPV16 E7 antigen.
The claims cover an assay-based detection method where disease presence is indicated by detecting or quantifying T cells that bind HPV16 CTL epitopes using an MHC tetramer assay, with coverage extending to short CTL epitope sequences from HPV16 E2, and in dependent coverage from HPV16 E6 and/or HPV16 E7.
Stated Advantages
Provides a method for detecting an HPV-16-associated disease by detecting or quantifying CTL epitope-binding T cells.
Documented Applications
Diagnosis of HPV16-associated disease in a subject using an MHC tetramer assay with T cells.
Immunotherapy context is described as using the disclosed immunogenic epitopes and CTL epitope-specific T cells, including a combined immune checkpoint blockade strategy.
Interested in licensing this patent?