Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 µg per peptide dose, the 50 µg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed. Overall, the histological regression rates were 50% at the 50 µg dose (7 of 14) and 100 µg dose (3 of 6), and 45 % overall (14 of 31). Of subjects in whom HPV type 16 (HPV 16) was detected at entry, it became undetectable in three subjects after vaccination, and the viral loads significantly decreased in nine subjects in whom HPV 16 infection was detected at entry and exit (p = 0.008). Immune profiling revealed increased T-helper type 1 cells after vaccinations (p = 0.02 and 0.0004 after 2 and 4 vaccinations, respectively). T-helper type 2 cells initially increased after two vaccinations (p = 0.01), but decreased below the baseline level after four vaccinations although not significantly. Pre-vaccination regulatory T cell levels were significantly lower in histological responders compared to non-responders (p = 0.03). Feasibility of testing plasma for multiplex cytokine/chemokine analysis and of performing proteomic analysis of PBMCs was examined for potentially identifying biomarkers in the future. While these analyses are feasible to perform, attention needs to be given to how soon the blood samples would be processed after phlebotomy. As sufficient safety of PepCan has been demonstrated, enrollment for the Phase II clinical trial has been opened.

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.

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 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 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.

Reducing perceived pain levels during nonbreast lymphoscintigraphy.

PURPOSE: The aim of this study was to quantify the reduction of perceived pain levels during lymphoscintigraphy for melanoma by altering the pH of the Tc-sulfur colloid to near the physiologic value of 7.40. PATIENTS AND METHODS: This is an institutional review board- and Food and Drug Administration-approved randomized, double-blinded, prospective crossover trial, registered with clinicaltrials.org. Before beginning the procedure and after signing informed consent, 60 serial enrollees presenting for sentinel lymph node imaging of melanoma of the thorax and appendicular structures completed a questionnaire addressing background information, administered by a research support nurse.An investigator (N.H.) prepared the injections to be used and labeled them such that no one else could discover which injections contained standard-of-care solution and which contained the pH-altered solution (buffered to near pH 7.40 using sodium bicarbonate).After each injection, the enrollee was asked by a research support nurse to quantify the pain of each injection using a scale of 0 to 10. The injection site location (head, thorax, appendicular structures, and other) was also recorded. RESULTS: Sixty subjects were enrolled in the study, of which 57 had complete data. On average, there was a significant mean (SD) decrease of 1.42 (2.17) points (95% confidence interval, 0.85-2.00) on a pain scale of 0 to 10 when the buffered injections were used as compared with the standard-of-care injections (P < 0.0001). Ordering of injections did not significantly affect perceived pain scores. CONCLUSIONS: The use of sodium bicarbonate to buffer the pH of Tc-sulfur colloid to near the physiologic value of 7.40 significantly reduced perceived pain levels during nonbreast lymphoscintigraphy.