Pap screening and surgical removal of cervical intraepithelial neoplasia (CIN2/3) has greatly reduced the incidence of cervical cancer, but testing lacks precision and the LEEP/conization procedure to excise these pre-cancerous lesions is associated with cervical incompetence and premature births. Recently co-testing for high risk HPV DNAs and specifically for HPV16 in cytologic samples has been broadly implemented to improve the accuracy of screening, particularly for equivocal cytologic diagnoses, and co-testing in women of 30 or more years. Since half of all persistent HPV16 infections progress to CIN2, HPV16+ women with normal cytology (negative for intraepithelial lesion and malignancy, NILM) undergo repeat co-testing in one year per ASCCP guidelines. If HPV16+ NILM again, these women undergo colposcopy. This screening identifies large numbers of women 30 years and over with persistent HPV16 infections who are likely to eventually progress and need surgical intervention, with continued potential for transmission or the development of neoplasia at the cervix and other anogenital sites, and suffering considerable psychosocial stress. Our overall goal is to develop a regimen to safely and effectively elicit immune clearance of persistent cervical HPV16 infections for secondary prevention of cervical cancer, an important unmet medical need. Intra-muscular administration of an HPV16 E6E7L2 fusion protein (termed TA-CIN) alone had little impact on HPV16+high grade disease. Recent studies suggest that the adjuvant GPI-0100 potently enhances cellular immune responses to TA-CIN vaccination, the importance of their targeting to the disease site, and the impact of imiquimod on the local microenvironment in disease clearance. We hypothesize that local inflammation and antigen-delivery to relevant draining lymph nodes is required for effective genital tract immunity. Thus we propose to administer TA-CIN formulated with GPI-0100 adjuvant in the cervix of women with persistent HPV16 infections but normal cytology to recruit HPV-specific immune cells to the genital tract, with or without priming the local microenvironment by topical administration of imiquimod on the cervix immediately following vaccination.
Oncogenic HPV infection, notably HPV16, is the cause of 10% of cancers in women worldwide, predominantly cervical cancer. Here we are developing a treatment regimen to trigger immune clearance of persistent genital HPV16 infections before they can progress to (pre-) cancer.
|Yang, Andrew; Farmer, Emily; Lin, John et al. (2016) The current state of therapeutic and T cell-based vaccines against human papillomaviruses. Virus Res :|
|Yang, Andrew; Farmer, Emily; Wu, T C et al. (2016) Perspectives for therapeutic HPV vaccine development. J Biomed Sci 23:75|
|Khan, Michelle J; Massad, L Stewart; Kinney, Walter et al. (2016) A common clinical dilemma: Management of abnormal vaginal cytology and human papillomavirus test results. Gynecol Oncol 141:364-70|
|Khan, Michelle J; Massad, L Stewart; Kinney, Walter et al. (2016) A Common Clinical Dilemma: Management of Abnormal Vaginal Cytology and Human Papillomavirus Test Results. J Low Genit Tract Dis 20:119-25|
|Jiang, Rosie T; Schellenbacher, Christina; Chackerian, Bryce et al. (2016) Progress and prospects for L2-based human papillomavirus vaccines. Expert Rev Vaccines 15:853-62|
|Wang, Yi-Shu; Chen, Jianfeng; Cui, Fengmei et al. (2016) LKB1 is a DNA damage response protein that regulates cellular sensitivity to PARP inhibitors. Oncotarget :|
|Sun, Yun-Yan; Peng, Shiwen; Han, Liping et al. (2016) Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract. Clin Cancer Res 22:657-69|
|Jones, Jacqueline; Mukherjee, Angana; Karanam, Balasubramanyam et al. (2016) African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression. Cancer Lett 380:513-22|
|Randles, Leah; Anchoori, Ravi K; Roden, Richard B S et al. (2016) The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle Progression. J Biol Chem 291:8773-83|
|Yang, Andrew; Jeang, Jessica; Cheng, Kevin et al. (2016) Current state in the development of candidate therapeutic HPV vaccines. Expert Rev Vaccines 15:989-1007|
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