OBJECTIVE: The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. METHODS: Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. RESULTS: Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. CONCLUSION: pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy.
OBJECTIVE: The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. METHODS: Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. RESULTS: Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. CONCLUSION: pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy.
Authors: Ellen E Sheets; Robert G Urban; Christopher P Crum; Mary Lynne Hedley; Joseph A Politch; Michael A Gold; Laila I Muderspach; Geoffrey A Cole; Peggy A Crowley-Nowick Journal: Am J Obstet Gynecol Date: 2003-04 Impact factor: 8.661
Authors: Francisco Garcia; Karl Ulrich Petry; Laila Muderspach; Michael A Gold; Patricia Braly; Christopher P Crum; Marianne Magill; Michael Silverman; Robert G Urban; Mary Lynne Hedley; Kathleen J Beach Journal: Obstet Gynecol Date: 2004-02 Impact factor: 7.661
Authors: Patti E Gravitt; Cheri Peyton; Cosette Wheeler; Raymond Apple; Russell Higuchi; Keerti V Shah Journal: J Virol Methods Date: 2003-09 Impact factor: 2.014
Authors: Patrick Schaerli; Lisa Ebert; Katharina Willimann; Andrea Blaser; Regula Stuber Roos; Pius Loetscher; Bernhard Moser Journal: J Exp Med Date: 2004-05-03 Impact factor: 14.307
Authors: Julie Ahn; Shiwen Peng; Chien-Fu Hung; Richard B S Roden; Tzyy-Choou Wu; Simon R Best Journal: Laryngoscope Date: 2017-07-17 Impact factor: 3.325
Authors: Paul Nghiem; William W Kwok; David M Koelle; Natalie V Longino; Junbao Yang; Jayasri G Iyer; Dafina Ibrani; I-Ting Chow; Kerry J Laing; Victoria L Campbell; Kelly G Paulson; Rima M Kulikauskas; Candice D Church; Eddie A James Journal: Cancer Immunol Res Date: 2019-08-12 Impact factor: 11.151
Authors: Benjamin Y Jin; Tracy E Campbell; Lindsey M Draper; Sanja Stevanović; Bianca Weissbrich; Zhiya Yu; Nicholas P Restifo; Steven A Rosenberg; Cornelia L Trimble; Christian S Hinrichs Journal: JCI Insight Date: 2018-04-19