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DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety, and immunogenicity of INO-3107

Author

Listed:
  • Matthew P. Morrow

    (Inovio Pharmaceuticals)

  • Elisabeth Gillespie

    (Inovio Pharmaceuticals)

  • Albert Sylvester

    (Inovio Pharmaceuticals)

  • Milan R. Amin

    (New York)

  • Peter C. Belafsky

    (University of California)

  • Simon R. Best

    (Johns Hopkins University School of Medicine)

  • Aaron D. Friedman

    (University of Cincinnati Medical Center)

  • Adam M. Klein

    (Emory University)

  • David G. Lott

    (Mayo Clinic Arizona)

  • Ted Mau

    (University of Texas Southwestern Medical Center)

  • Randal C. Paniello

    (Washington University School of Medicine)

  • Seth M. Pransky

    (Pediatric Specialty Partners)

  • Nabil F. Saba

    (Emory University)

  • Grace S. Tan

    (Inovio Pharmaceuticals)

  • Sadie Wisotsky

    (Inovio Pharmaceuticals)

  • Sarah A. Marcus

    (Inovio Pharmaceuticals)

  • Emma L. Reuschel

    (Inovio Pharmaceuticals)

  • Katherine S. Reed

    (Inovio Pharmaceuticals)

  • David B. Weiner

    (The Wistar Institute)

  • Michael Dallas

    (Inovio Pharmaceuticals)

  • Jeffrey M. Skolnik

    (Inovio Pharmaceuticals)

Abstract

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response.

Suggested Citation

  • Matthew P. Morrow & Elisabeth Gillespie & Albert Sylvester & Milan R. Amin & Peter C. Belafsky & Simon R. Best & Aaron D. Friedman & Adam M. Klein & David G. Lott & Ted Mau & Randal C. Paniello & Seth, 2025. "DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety, and immunogenicity of INO-3107," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56729-6
    DOI: 10.1038/s41467-025-56729-6
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