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DNA免疫疗法（INO-3107）在HPV-6/11型复发性呼吸道乳头状瘤病中通过增强免疫原性支持的长期疗效

DNA Immunotherapy (INO-3107) Long-Term Efficacy Supported by Enhanced Immunogenicity in HPV-6/11 RRP.

临床研究咽喉科IF 2.3Q2

文献信息

PMID42963203
原文在 PubMed 查看原文 ↗
发表日期2026
作者Milan R Amin
查看其他 15 位作者

Peter C Belafsky；Simon R Best；Aaron D Friedman；Adam M Klein；David G Lott；Ted Mau；Randal C Paniello；Seth M Pransky；Nabil F Saba；Stefani A Slog；Elisabeth Gillespie；Christopher Welsh；Michael Dallas；Matthew P Morrow；Jeffrey M Skolnik

作者单位Department of Otolaryngology-Head and Neck Surgery, New York University Grossman School of Medicine, New York, New York, USA.
查看其他 10 条单位信息

Department of Otolaryngology-Head and Neck Surgery, Davis School of Medicine, University of California, Sacramento, California, USA.；Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.；Division of Laryngology, Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.；Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.；Division of Laryngology, Mayo Clinic Arizona, Phoenix, Arizona, USA.；Division of Laryngology, Department of Otolaryngology-Head and Neck Surgery, Voice Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.；Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.；Pediatric Specialty Partners of San Diego, San Diego, California, USA.；Department of Hematology and Medical Oncology, the Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.；Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.

期刊The Laryngoscope
SCI 分区Q2
IF2.3
研究类型临床研究 · 临床
所属专科咽喉科

中文摘要

目的： 复发性呼吸道乳头状瘤病（RRP）由慢性HPV-6/11感染引起，导致乳头状瘤反复生长，需要频繁手术切除。DNA免疫疗法INO-3107旨在诱导HPV抗原特异性T细胞反应并减少手术负担。本分析评估了INO-3107后HPV特异性免疫反应及其与长期临床结局的关联。
方法： 患有HPV-6/11相关RRP的成人在一项1/2期试验中接受INO-3107治疗，并随访一年，并在长期扩展研究中进行额外临床随访。将第1年和第2年的手术次数与治疗前一年进行比较。分析第0天和第1年采集的血液和喉气管组织，以评估治疗相关的T细胞活性变化。全程评估安全性。
结果： 32例患者接受治疗；28例继续进入第2年。在第1年，大多数可评估患者显示T细胞活性增加：73%（19/26）在外周血中显示持续扩增的T细胞群，71%（12/17）在喉气管组织中显示更高的T细胞克隆计数，表明部位特异性免疫浸润。抗病毒T细胞特征在CD4+ Th1和CD8+细胞毒性中富集达88%，在CD8+效应记忆细胞中达71%，提示气道组织中持久的促炎和记忆反应。总体人群中平均年手术次数随时间下降（基线：4.1，第1年：1.7，第2年：0.9）。在应答者亚组中也观察到类似的持久下降。INO-3107耐受良好，无治疗相关严重不良事件。
结论： INO-3107产生增加的HPV导向T细胞反应，并在两年内大幅减少手术操作，支持其能够在给药窗口期间无需额外手术的情况下为RRP提供长期临床获益。

英文摘要

OBJECTIVES: Recurrent respiratory papillomatosis (RRP), caused by chronic HPV-6/11 infection, leads to repeated papilloma growth requiring frequent surgical removal. DNA immunotherapy INO-3107 aims to induce HPV antigen-specific T-cell responses and reduce surgical burden. This analysis evaluated HPV-specific immune responses after INO-3107 and their association with long-term clinical outcomes.
METHODS: Adults with HPV-6/11-associated RRP received INO-3107 in a Phase 1/2 trial and were followed for one year, with additional clinical follow-up in a long-term extension. Number of surgeries in Years 1 and 2 was compared with the pre-treatment year. Blood and laryngotracheal tissue collected at Day 0 and Year 1 were analyzed for treatment-related changes in T-cell activity. Safety was assessed throughout.
RESULTS: Thirty-two patients were treated; 28 continued into Year 2. At Year 1, most evaluable patients showed increased T-cell activity: 73% (19/26) demonstrated persistent expanded T-cell populations in blood, 71% (12/17) showed higher T-cell clone counts in laryngotracheal tissue, indicating site-specific immune infiltration. Antiviral T-cell signatures were enriched in 88% for CD4+ Th1 and CD8+ cytotoxic, and 71% for CD8+ effector memory, suggesting durable proinflammatory and memory responses in airway tissue. Mean annual surgeries decreased over time in the overall population (Baseline: 4.1, Year 1: 1.7, Year 2: 0.9). Similar durable reductions were observed in Responder subgroups. INO-3107 was well-tolerated, with no treatment-related serious adverse events.
CONCLUSION: INO-3107 generates increased HPV-directed T-cell responses and substantially reduced surgical procedures over two years, supporting its ability to provide long-term clinical benefit in RRP without requiring additional surgeries during the dosing window.