Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3

Author:

Kawana Kei1ORCID,Kobayashi Osamu1,Ikeda Yuji1,Yahata Hideaki2,Iwata Takashi3ORCID,Satoh Toyomi4,Akiyama Azusa4,Maeda Daichi5,Hori-Hirose Yumiko6,Uemura Yukari7,Nakayama-Hosoya Kaori8,Katoh Kanoko1,Katoh Yuki9,Nakajima Takahiro1,Taguchi Ayumi10,Komatsu Atsushi1,Asai-Sato Mikiko1,Tomita Naoko1,Kato Kiyoko2,Aoki Daisuke3ORCID,Igimi Shizunobu11,Kawana-Tachikawa Ai8,Schust Danny J12

Affiliation:

1. Department of Obstetrics and Gynecology, Nihon University School of Medicine , Tokyo, Japan

2. Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University , Fukuoka, Japan

3. Department of Obstetrics and Gynecology, Keio University School of Medicine , Tokyo, Japan

4. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba , Ibaraki, Japan

5. Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University , Ishikawa, Japan

6. Department of Central Laboratory and Surgical Pathology, National Hospital Organization Osaka National Hospital , Osaka, Japan

7. Department of Data Science, Center for Clinical Science, National Center for Global Health and Medicine , Tokyo, Japan

8. AIDS Research Center, National Institute of Infectious Diseases , Tokyo, Japan

9. Department of Functional Morphology, Nihon University School of Medicine , Tokyo, Japan

10. Laboratory of Human Single Cell Immunology, World Premier International Immunology Frontier Research Center , Osaka, Japan

11. Department of Applied Biology and Chemistry, Tokyo University of Agriculture , Tokyo, Japan

12. Department of Obstetrics and Gynecology, Duke University , Durham, NC, USA

Abstract

Abstract Background Although many human papillomavirus (HPV)–targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. Methods In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16–positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. Results In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7–specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. Conclusion This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16–positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. Trial registration jRCT2031190034.

Funder

GLOVACC Co Ltd

Japan Agency for Medical and Development

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Reference29 articles.

1. Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis;Bruni;Lancet Glob Health,2016

2. HPV vaccination: an underused strategy for the prevention of cancer;Shapiro;Curr Oncol,2022

3. HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010-2019;Bruni;Prev Med,2021

4. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease;Kyrgiou;Cochrane Database Syst Rev,2017

5. Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases;Skeate;Hum Vaccin Immunother,2016

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