T-cell Receptor Targeting Human Papillomavirus-16 E6 Oncoprotein

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 E6 oncoprotein that drives malignant transformation in HPV-infected cells. Further, E6 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 E629-38. The inventors successfully transduced T cells obtained from peripheral blood mononuclear cells (PBMCs) with this TCR. 

  The NCI Center for Immuno-Oncology is actively seeking co-development partners and/or licensees for this E6-targeting TCR with therapeutic potential for HPV-positive conditions.