SUPPLEMENTARY INFORMATION:

Recurrent Respiratory Papillomatosis (RRP) and anogenital condyloma arise from chronic infection with human papillomavirus (HPV) 6 or 11. They can cause significant morbidity due to persistent papillomatous growths in the upper aerodigestive or anogenital tract. In RRP, lesions may obstruct the airway (leading to dysphonia), dyspnea, recurrent pneumonia, or pulmonary failure. In rare cases, it may progress to malignancy. Current treatment options for RRP include zopapogene imadenovec (Papzimeos), systemic bevacizumab, and repeated surgical debulking. Papzimeos can lead to durable responses in some patients but remains ineffective against pulmonary disease. Systemic bevacizumab can control disease, but prolonged use can lead to intolerable toxicities. Repeat surgical debulking causes cumulative surgical and anesthetic risks. Therefore, there remains a critical unmet need for ( printed page 54729) safe and effective therapies for patients with aggressive or pulmonary RRP refractive to standard-of-care treatments.

Researchers at the NCI identified several T cell receptors (TCRs) with potential utility in adoptive cell therapy and other TCR-based approaches to treat HPV 6- or HPV 11-associated diseases—including RRP. These TCRs used engineered T cells derived from peripheral blood mononuclear cells (PBMCs), an easily accessible source of human immune cells. The engineered T cells demonstrated reproducible, antigen-specific recognition of multiple HPV 6 and HPV 11 proteins presented by diverse HLA class I subtypes. The inventors further showed that these TCR-engineered T cells effectively eliminated HPV 6/11-infected target cells. Such results support the therapeutic potential of these TCRs for HPV-associated disease. The intellectual property rights have been assigned to the Government of the United States of America.

“This Notice is in accordance with 37 CFR 404.4 Authority to grant licenses.”

NIH Reference Number: E-002-2026-0.

Related Technologies: E-143-2024-0 and E-019-2025-0.

Product Type: Therapeutic.

Therapeutic Area(s): Immunology | Infectious Disease | Oncology.

Development Stage: Pre-clinical ( in vivo validation).

Publications: N/A.

Patent(s): Provisional patent application.

Potential Commercial Applications:

• Treatment and diagnosis of recurrent RRP and other premalignant and nonmalignant conditions.
  • Adoptive cell therapy.
  • TCR-based therapy.
  • Combination therapy.
• Treatment and diagnosis of additional HPV 6- or HPV 11-associated diseases and chronic infections.
  • Adoptive cell therapy.
  • TCR-based therapy.
  • Combination therapy.

Competitive Advantages:

• Novel adoptive cell therapies, either as monotherapies or in combination with other therapeutic modalities.
• Promising freedom to practice as part of a comprehensive intellectual property portfolio for RRP therapeutics and diagnostics.
• Established FDA regulatory precedent for TCR-based therapeutics.
• Opportunity to qualify for regulatory incentives for rare diseases, including: orphan drug designation, priority review, and breakthrough therapy designation.

Collaboration Opportunity: Researchers at the NCI seek licensing and/or co-development research collaborations for a collection of T-cell receptors (TCRs) that specifically target HPV 6 or HPV 11 antigens.

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