PMID- 26451301 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220321 IS - 2162-4011 (Print) IS - 2162-402X (Electronic) IS - 2162-4011 (Linking) VI - 4 IP - 10 DP - 2015 Oct TI - A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3. PG - e1031439 LID - e1031439 AB - 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 and Candida skin 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 mug 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 mug 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 that Candida, 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. FAU - Greenfield, William W AU - Greenfield WW AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Stratton, Shawna L AU - Stratton SL AD - College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Myrick, Rebecca S AU - Myrick RS AD - College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Vaughn, Rita AU - Vaughn R AD - College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Donnalley, Lisa M AU - Donnalley LM AD - College of Medicine; Translational Research Institute; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Coleman, Hannah N AU - Coleman HN AD - Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Mercado, Maria AU - Mercado M AD - Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Moerman-Herzog, Andrea M AU - Moerman-Herzog AM AD - Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Spencer, Horace J AU - Spencer HJ AD - Biostatistics; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Andrews-Collins, Nancy R AU - Andrews-Collins NR AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Hitt, Wilbur C AU - Hitt WC AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Low, Gordon M AU - Low GM AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Manning, Nirvana A AU - Manning NA AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - McKelvey, Samantha S AU - McKelvey SS AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Smith, Dora AU - Smith D AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Smith, Michael V AU - Smith MV AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Phillips, Amy M AU - Phillips AM AD - Departments of Obstetrics and Gynecology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Quick, C Matthew AU - Quick CM AD - Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Jeffus, Susanne K AU - Jeffus SK AD - Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Hutchins, Laura F AU - Hutchins LF AD - Medicine (Hematology-Oncology Division); University of Arkansas for Medical Sciences ; Little Rock, AR USA. FAU - Nakagawa, Mayumi AU - Nakagawa M AD - Pathology; University of Arkansas for Medical Sciences ; Little Rock, AR USA. LA - eng GR - R01 CA143130/CA/NCI NIH HHS/United States GR - UL1 TR000039/TR/NCATS NIH HHS/United States GR - P20 GM103625/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150527 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 PMC - PMC4590015 OTO - NOTNLM OT - T cells OT - cervical intraepithelial neoplasia OT - clinical trial OT - human papillomavirus OT - therapeutic vaccine EDAT- 2015/10/10 06:00 MHDA- 2015/10/10 06:01 PMCR- 2016/05/27 CRDT- 2015/10/10 06:00 PHST- 2015/02/06 00:00 [received] PHST- 2015/03/02 00:00 [revised] PHST- 2015/03/15 00:00 [accepted] PHST- 2015/10/10 06:00 [entrez] PHST- 2015/10/10 06:00 [pubmed] PHST- 2015/10/10 06:01 [medline] PHST- 2016/05/27 00:00 [pmc-release] AID - 1031439 [pii] AID - 10.1080/2162402X.2015.1031439 [doi] PST - epublish SO - Oncoimmunology. 2015 May 27;4(10):e1031439. doi: 10.1080/2162402X.2015.1031439. eCollection 2015 Oct.