title: A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine withCandidaskin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3.
abstract: PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein andCandidaskin test reagent as a novel adjuvant.PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide).RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P= 0.02).CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests thatCandida,which induces interleukin-12 (IL-12)in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted.
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Greenfield
authors.affiliation: College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Shawna L
authors.initials: SL
authors.lastname: Stratton
authors.affiliation: College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Myrick
authors.affiliation: College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Vaughn
authors.affiliation: College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Donnalley
authors.affiliation: Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Hannah N
authors.initials: HN
authors.lastname: Coleman
authors.affiliation: Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Mercado
authors.affiliation: Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Moerman-Herzog
authors.affiliation: Biostatistics; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Horace J
authors.initials: HJ
authors.lastname: Spencer
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Andrews-Collins
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Wilbur C
authors.initials: WC
authors.lastname: Hitt
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Gordon M
authors.initials: GM
authors.lastname: Low
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Nirvana A
authors.initials: NA
authors.lastname: Manning
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Samantha S
authors.initials: SS
authors.lastname: McKelvey
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Smith
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Smith
authors.affiliation: Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Phillips
authors.affiliation: Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: C Matthew
authors.initials: CM
authors.lastname: Quick
authors.affiliation: Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Jeffus
authors.affiliation: Medicine (Hematology-Oncology Division); University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Laura F
authors.initials: LF
authors.lastname: Hutchins
authors.affiliation: Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakagawa
keywords: T cells; cervical intraepithelial neoplasia; clinical trial; human papillomavirus; therapeutic vaccine