The epidermal growth factor receptor (EGFR) is an attractive target for cancer therapy because it is highly overexpressed and correlated with poor prognosis in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Although clinical responses have been achieved using EGFR inhibition through blocking antibodies or EGFR tyrosine-kinase inhibitors, many patients do not respond to these treatments. Because delivery of large molecules such as antibodies across the blood brain barrier is difficult, there exist a critical need for additional EGFR inhibition therapies.
Description
Investigators have identified and characterized novel EGFR tumor-associated antigen (TAA) epitopes and enhanced agonist epitopes. Preclinical studies indicate that these EGFR agonist epitopes bind HLA-A2 molecules at lower peptide concentrations and with higher stability compared to other predicted EGFR-TAAs. Further studies demonstrate that EGFR-specific T-cell lines generated against the EGFR-TAA induced higher levels of tumor killing agents and resulted in more efficient killing of human tumor cells overexpressing the EGFR-TAA. Thus, these agonist epitopes of EGFR have been incorporated into immunotherapy protocols, and may constitute an alternative and/or additional approach for the treatment of EGFR-expressing cancers.
Applications
• Incorporation into cell-based or other immunotherapeutic protocols
• Development of cancer vaccines
• Combination therapy with various anti-EGFR antibodies and small molecule inhibitors
Advantages
• Tumor-associated antigens can be incorporated into immunotherapy protocols as a single agent or in combination with other antigen epitopes, adjuvants, chemotherapy, or targeted small molecule or antibody therapies
Invention Readiness
Phase I clinical studies in patients with HNSCC
IP Status
https://patents.google.com/patent/US8367069B2
