Technology Bundle ID
NCI-E-176-2014

T-cell Receptor Targeting Human Papillomavirus-16 E7 Oncoprotein

Applications
Lead Inventors
Steven Rosenberg (NCI)
Co-Inventors
Christian Hinrichs (NCI)
Development Status
Clinical
ICs

Human papillomavirus (HPV) is a group of human viruses known to cause various malignancies. Of the group, HPV-16 is the most prevalent strain – an estimated 90% of adults have been exposed. HPV-16 is also the strain most commonly associated with malignancy, causing the vast majority of cervical, anal, vaginal, vulvar, and penile cancers. Currently, HPV-positive malignancies non-responsive to surgery or radiation are incurable and poorly palliated by existing systemic therapies. Thus, an alternative therapeutic approach for HPV-positive malignancies is needed. 

Researchers at the National Cancer Institute (NCI) developed a T cell receptor (TCR) that may be used in adoptive cell therapy to treat HPV-positive malignancies. The TCR confers high-avidity recognition of the HPV-specific E7 oncoprotein that drives malignant transformation in HPV-infected cells. Further, E7 is specific to and constitutively expressed by cancer cells, making it an ideal therapeutic target. The TCR targets human leukocyte antigen (HLA)-A*02-restricted epitope E711-19. The inventors successfully transduced T cells obtained from peripheral blood mononuclear cells (PBMCs) with this TCR. An ongoing Phase I/II clinical trial is investigating the efficacy of the E7-targeting TCR in treating HPV-positive malignancies.  

The NCI Center for Immuno-Oncology is actively seeking co-development partners and/or licensees for this E7-targeting TCR with therapeutic potential for HPV-positive conditions.  

Commercial Applications
  • Adoptive cell therapy against HPV-positive cancers
  • Treatment of HPV-related infections and premalignant conditions
  • Prevention of HPV-related infections and premalignant conditions
  • Detection of HPV-infected or transformed cells for diagnostic purposes

 

Competitive Advantages
  • FDA approval of another first-in-class TCR therapeutic demonstrates treatment benefit of approach 
  • FDA approval of another first-in-class TCR therapeutic decreases regulatory risk
  • High avidity for the HPV-specific E7 oncoprotein
  • Specifically recognize HLA-A*02-positive HPV-16 cancer cells
  • TCR can be used to transduce T cells isolated from PBMCs, an easily accessible source of human immune cells 

 

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