A phase 1/2a, dose-escalation, safety and preliminary efficacy study of oral therapeutic vaccine in subjects with cervical intraepithelial neoplasia 3

Young Chul Park, Yung Taek Ouh, Moon Hee Sung, Hong Gyu Park, Tae Jin Kim, Chi Heum Cho, Jong Sup Park, Jae Kwan Lee

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    22 Citations (Scopus)

    Abstract

    Objective: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus case in patients with CIN 3. Methods: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. Results: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. Conclusions: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3.

    Original languageEnglish
    Article numbere88
    JournalJournal of gynecologic oncology
    Volume30
    Issue number6
    DOIs
    Publication statusPublished - 2019 Nov

    Bibliographical note

    Funding Information:
    This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1023). Conflict of Interest Young-Chul Park, Moon-Hee Sung, Hong-Gyu Park from BioLeaders, Corp. are employees of and/or shareholders of the company, which is developing BLS-M07 vaccine. The remaining authors declare no competing financial interests. We thank all members of research team in BioLeaders, Corp., for technical support.

    Funding Information:
    This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI14C1023). Conflict of Interest Young-Chul Park, Moon-Hee Sung, Hong-Gyu Park from BioLeaders, Corp. are employees of and/or shareholders of the company, which is developing BLS-M07 vaccine. The remaining authors declare no competing financial interests.

    Publisher Copyright:
    © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

    Keywords

    • Cervical Intraepithelial Neoplasia
    • Papillomavirus E7 Proteins
    • Papillomavirus Vaccines

    ASJC Scopus subject areas

    • Oncology
    • Obstetrics and Gynaecology

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