Objective: To show that E6-induced proteasomal degradation of p53 in human papillomavirus (HPV) 16–positive head and neck squamous cell carcinoma enhances cytotoxic T-lymphocyte recognition and lysis mediated by increased HLA-A2-p53(264-272) complexes. By directly targeting E7 and p53, we can increase efficacy of adjuvant immunotherapy by avoiding viral mutation and the potential loss of a target.
Design: Adjuvant treatment was 5% imiquimod cream (Aldara) or aqueous imiquimod, a toll-like receptor 7 agonist and Food and Drug Administration–approved topical immunomodulatory treatment for HPV-associated warts. Initial in vivo work with murine H2-Kb and -Db restricted peptides, p53(158-166) and E7(49-57), respectively, compared subcutaneous delivery with or without subcutaneous aqueous imiquimod. Current in vivo vaccination models use the HLA-A2 restricted peptides E7(11-20) and p53(261-269), the murine homologue of human HLA-A2 restricted p53(264-272).
Kim H, Wang J, Lopez-Albaitero A, Ferris RL. P181 Combination Tumor Antigen–Targeted Immunotherapy in HPV-16–Positive Head and Neck Squamous Cell Carcinoma. Arch Otolaryngol Head Neck Surg. 2006;132(8):900. doi:10.1001/archotol.132.8.900-b