Ikeda Yuji, Adachi Katsuyuki, Tomio Kensuke, Eguchi-Kojima Satoko, Tsuruga Tetsushi, Uchino-Mori Mayuyo, Taguchi Ayumi, Komatsu Atsushi, Nagamatsu Takeshi, Oda Katsutoshi, Kawana-Tachikawa Ai, Uemura Yukari, Igimi Shizunobu, Osuga Yutaka, Fujii Tomoyuki, Kawana Kei
Department of Obstetrics and Gynecology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Vaccines (Basel). 2021 Apr 1;9(4):329. doi: 10.3390/vaccines9040329.
Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV); high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose; however, only in the GLBL101c group, two patients had complete regression (CR; regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel -based vaccine with stronger immunogenicity than GLBL101c should be developed.
宫颈上皮内瘤变（CIN）是宫颈癌的前驱病变，由高危型人乳头瘤病毒（HPV）引起；高级别CIN病变（CIN2-3）为癌前病变，需要治疗。目前尚无全球批准的用于治疗CIN2-3的疗法。本研究是一项安慰剂对照的随机临床试验，对40例HPV16阳性的CIN2患者进行GLBL101c治疗，这些患者按1:1随机分组，在第1、2、4和8周接受GLBL101c（1克/天）或安慰剂治疗5天。GLBL101c组和安慰剂组在患者背景和不良事件方面未观察到差异。此外，在主要终点，即首次口服给药16周后的病理消退方面，两组之间未观察到统计学上的显著差异；然而，仅在GLBL101c组中，有两名患者实现了完全消退（CR；16周内恢复正常）。使用宫颈淋巴细胞（CxLs）或外周血单个核细胞通过干扰素γ酶联免疫斑点（IFNγ-ELISPOT）测定法鉴定的斑点数量与IFNγ产生显著相关。在两例CR病例中，在第16周观察到了E7特异性Th1免疫反应。因此，我们得出结论，应开发一种比GLBL101c具有更强免疫原性的新型疫苗。
