HPV-specific CD8 TCR Sequences

Tumor Specific CD8 T Cell TCR Sequences of HPV-Positive Head and Neck Tumors

Application

HPV-specific CD8 TCR sequences for the treatment of HPV-positive head and neck cancer by adoptive cell therapy.

Key Benefits

HPV tumor antigen set is specific for HPV-positive head and neck cancer.
Targeting of ‘non-classical’ HPV antigens E2 and E5.
Potential to synergize and complement HPV E6/7-specific TCR therapies currently undergoing clinical trials.

Market Summary

Human papillomavirus (HPV) causes nearly all cervical cancers and others of the vagina, vulva, penis, anus, and head & neck. Although three HPV vaccines have been approved and are highly effective in protecting against HPV-induced cancers, those who forego or are not able to be vaccinated are susceptible to these devastating cancers. Hence, there is a significant unmet need to develop new therapies to treat the millions of people suffering from HPV and other virally induced cancers.

Technical Summary

HPV-positive head and neck cancer tumor cells express HPV proteins that can be recognized by CD8 T cells. Researchers at Emory identified HPV-specific CD8 T cell epitopes derived from the HPV E2 and E5 proteins and determined the TCR sequences of HPV-specific CD8 T cells in tumor and metastasized lymph nodes of 6 patients with HPV+ head and neck cancer. The analysis pipeline used by the inventors to identify HPV-specific CD8 T cell epitopes consisted of in vitro T cell expansion using predicted epitopes of the most prevalent HPV type and a combination of biological and biochemical analyses culminating in the generation and testing of MHC-I tetramers and determination of the HPV-specific CD8 T cell TCR sequences by single cell RNAseq.