SEQUENCE LISTING

The present specification makes reference to a Sequence Listing (submitted electronically as a .txt file named “208192-9044_ST25.txt.” The .txt file was generated on Nov. 13, 2018 and is 10,491 bytes in size. The entire contents of the Sequence Listing are hereby incorporated by reference.

TECHNICAL FIELD

Embodiments of the present disclosure pertain generally to cancers associated with 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 HPV16-associated cancers.

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with close to 600,000 cases diagnosed annually. A subset of HNSCCs caused by the human papillomavirus (HPV), (HPV+ HNSCCs), are molecularly and clinically distinct from non-HPV associated HNSCCs (HPV− HNSCCs). In the United States, 70-80% of HPV+ HNSCCs are caused by the oncogenic HPV type 16 (HPV16). Incidence of HPV+ HNSCC increased 225% from 1984-2004 and has now surpassed the incidence of cervical cancer. Although HPV vaccines effectively prevent HPV-related cancers, the impact of vaccination on HNSCC incidence may not occur until 2060, likely due in part to slow vaccine uptake, and the decades between infection and clinical HPV+ HNSCC diagnosis. As a result, over 600,000 cases are predicted in the interim, providing a strong rationale for the development of novel therapeutic strategies against HPV+ HNSCC.

The recent development of clinically effective tumor immunotherapies, such as checkpoint blockade (CKB) using PD-1/PD-L1 inhibitors, has led to FDA approval of nivolumab and pembrolizumab for HNSCC. It is now established that the clinical response to CKB is correlated with tumor neo-epitope load. Tumor-specific neo-epitopes have been directly targeted using therapeutic vaccines and/or adoptive T-cell therapy (ACT), and have been shown to enhance cytotoxic T-cell targeting of multiple solid tumors. Thus, there is a renewed interest in defining the human leukocyte antigen (HLA) restricted antigenic repertoire of tumor infiltrating lymphocytes (TILs) to develop targeted therapeutic vaccines, to identify T-cell receptors (TCR) for ACT, and to monitor clinical responses to complex cancer immunotherapies.

SUMMARY

Embodiments of the present disclosure pertain generally to cancers associated with 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 HPV16-associated cancers.

Embodiments of the present disclosure include an immunogenic composition for treating a subject having a HPV16-associated disease. In accordance with these embodiments the composition includes a synthetic polypeptide encoding a cytotoxic T lymphocyte (CTL) epitope derived from E2, E6, or E7 human papillomavirus subtype 16 (HPV16) antigens and a pharmaceutically acceptable carrier or excipient. In some embodiments, the immunogenic composition is for treating a subject with head and neck squamous cell carcinoma (HNSCC).

Embodiments of the present disclosure include a method of treating a subject having a HPV16-associated disease. In accordance with these embodiments, the method comprises administering an immunogenic composition described above wherein the administration of the composition induces an immune response against the HPV16-associated disease and treats the subject. In some embodiments the method is used to treat a subject with head and neck squamous cell carcinoma (HNSCC). In some embodiments, the immunogenic composition includes an immune checkpoint inhibitor which can include a programmed cell death protein 1 (PD-1) and an Indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor.

Embodiments of the present disclosure include an immune cell comprising a T-cell receptor (TCR) capable of binding a synthetic polypeptide encoding a cytotoxic T lymphocyte (CTL) epitope derived from E2, E6, or E7 human papillomavirus subtype 16 (HPV16) antigens.

Embodiments of the present disclosure include a method of detecting an HPV16-associated disease in a subject. In accordance with these embodiments, the method includes obtaining a biological sample comprising T cells from a subject, contacting the biological sample with a MHC class I peptide tetramer composition comprising at least one synthetic MHC class I molecule bound to at least one synthetic polypeptide encoding a cytotoxic T lymphocyte (CTL) epitope derived from E2, E6, or E7 human papillomavirus subtype 16 (HPV16) antigens and detecting the presence of T cells bound to the synthetic polypeptide. In some embodiments the detection comprises flow cytometry or fluorescence-activated cell sorting.

