We have shown that cluster intradermal vaccination of CRT/E7DNA (with a short interval between vaccinations) more rapidly induced E7-specific immune responses and generated better therapeutic effects against E7-expresslng tumors compared to DNA vaccination with longer intervals. These findings prompted us to propose a phase I trial to investigate whether the repeated, cluster intradermal CRT/E7 DNA vaccination is safe and can generate E7-specific CD8+ T cell immune responses in patients with HPV-16 associated stage 1B1 resectable cervical cancer. We plan to vaccinate two cohorts of patients, one before and one after tumor resection. The proposed trial using cluster vaccination regimen permits us to complete the vaccination regimen before tumor resection allowing us to assess the influence of DNA vaccination on tumor microenvironment without compromising the standard care. Clinical grade pNGVL4a-CRT/E7(detox) DNA vaccine has been manufactured by NCI RAID program and formulated in the proprietary ND-10 gene gun device by PowderMed/Pfizer for intradermal vaccination. The proposed trial will be performed at the University of Alabama at Birmingham, which has one of the highest populations of stage IBl cervical cancer patients. Specifically, we plan to:
Aim 1 Evaluate the safety/toxiclty associated with repeated, cluster intradermal pNGVL4a-CRT/E7 (detox) DNA vaccination via gene gun in patients with HPV 16-associated stage IBl cervical cancer, using a dose-escalating regimen;
Aim 2. Characterize systemic HPV-16 E6 and E7-speciflc humoral and T cell-mediated immune responses in stage IBl cervical cancer patients receiving the DNA vaccination via gene gun;
Aim 3. Characterize the presence of HPV-16 E6 and E7-speclfic CD8+ T cell immune responses in the tumor and draining lymph nodes in selected stage IBl cervical cancer patients receiving the DNA vaccination via gene gun;
Aim 4. Determine the subset population of immune cells infiltrating the tumor bed, B7H-1 and STAT-3 expression in tumor microenvironment and to determine the apoptotic tumor cell death in stage IB1 cervical cancer patients receiving the DNA vaccination via gene gun. The successful implementation of the proposed study will allow us to assess the systemic and local antigen-specific immune responses following repeated cluster intradermal DNA vaccination using the ND-10 gene gun device in HPV-16 associated stage IBl cervical cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
United States
Zip Code
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

Showing the most recent 10 out of 251 publications