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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.
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BACKGROUND: The Fli-1 transcription factor functions in cellular proliferation and tumorigenesis. Its role in various neoplasms and its presence in lymphocytes suggest a link between Fli-1 dysregulation and the pathogenesis of mycosis fungoides (MF). In this study, we further elucidate this possible link. METHODS: Sections from archived specimens were stained using a polyclonal antibody against Fli-1. The percentage of nuclei showing Fli-1 expression was recorded. These were compared with reactive dermatoses. RESULTS: All of the tumor stage lesions showed high levels of nuclear Fli-1 expression. Of plaque stage lesions, six of 12 (50%) showed the same intensity, while the remaining six of 12 varied significantly in their Fli-1 expression. The few patch stage lesions also showed varied expression. CONCLUSION: This study shows diffuse nuclear expression of Fli-1 in all tumor stage MF, whereas expression of this transcription factor varied widely in the early, epidermotropic stages. Although the numbers are too small to draw statistical significance, this study demonstrates an association between increased expression of Fli-1 and progression to tumor stage MF that merits further investigation. Additionally, the mixed expression of Fli-1 in the epidermotropic stages suggests that the role of Fli-1 in MF is related to neoplasia and not epidermotropism.
