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

被引：11

作者：

Kawana, Kei ^{[1
]}

Kobayashi, Osamu ^{[1
]}

Ikeda, Yuji ^{[1
]}

Yahata, Hideaki ^{[2
]}

Iwata, Takashi ^{[3
]}

Satoh, Toyomi ^{[4
]}

Akiyama, Azusa ^{[4
]}

Maeda, Daichi ^{[5
]}

Hori-Hirose, Yumiko ^{[6
]}

Uemura, Yukari ^{[7
]}

Nakayama-Hosoya, Kaori ^{[8
]}

Katoh, Kanoko ^{[1
]}

Katoh, Yuki ^{[9
]}

Nakajima, Takahiro ^{[1
]}

Taguchi, Ayumi ^{[10
]}

Komatsu, Atsushi ^{[1
]}

Asai-Sato, Mikiko ^{[1
]}

Tomita, Naoko ^{[1
]}

Kato, Kiyoko ^{[2
]}

Aoki, Daisuke ^{[3
]}

Igimi, Shizunobu ^{[11
]}

Kawana-Tachikawa, Ai ^{[8
]}

Schust, Danny J. ^{[12
]}

机构：

[1] Nihon Univ, Sch Med, Dept Obstet & Gynecol, 30-1 Oyaguchi Kamimachi,Itabashi Ku, Tokyo 1738610, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Obstet & Gynecol, Fukuoka, Japan

[3] Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo, Japan

[4] Univ Tsukuba, Fac Med, Dept Obstet & Gynecol, Ibaraki, Japan

[5] Kanazawa Univ, Grad Sch Med Sci, Dept Mol & Cellular Pathol, Kanazawa, Ishikawa, Japan

[6] Natl Hosp Org Osaka Natl Hosp, Dept Cent Lab & Surg Pathol, Osaka, Japan

[7] Natl Ctr Global Hlth & Med, Dept Data Sci, Ctr Clin Sci, Tokyo, Japan

[8] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan

[9] Nihon Univ, Sch Med, Dept Funct Morphol, Tokyo, Japan

[10] World Premier Int Immunol Frontier Res Ctr, Lab Human Single Cell Immunol, Osaka, Japan

[11] Tokyo Univ Agr, Dept Appl Biol & Chem, Tokyo, Japan

[12] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA

来源：

JNCI CANCER SPECTRUM | 2023年 / 7卷 / 06期

关键词：

HPV TYPE-16 E7; T-CELLS; IMMUNE-RESPONSES; IMMUNOTHERAPY; REGRESSION; IMMUNIZATION; STRATEGY; INDUCE;

D O I：

10.1093/jncics/pkad101

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-gamma 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.

引用

页数：9

共 29 条

[1] Oral immunization with a Lactobacillus casei vaccine expressing human papillomavirus (HPV) type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocytes against HPV16 E7 [J].