Human papillomavirus type 16 E6 oncoprotein-specific T-cell receptor (HPV-16 E6 TCR) (HPV-16 E6 TCR)

The Human papillomavirus type 16 (HPV-16) E6 oncoprotein-specific T-cell receptor (TCR) is a recombinant or naturally derived immune receptor used in adoptive cell therapy to treat HPV-associated malignancies (Draper et al., 2015, Clin Cancer Res). HPV-16 E6 is a critical viral oncoprotein that drives cancer by binding to and promoting the degradation of the p53 tumor suppressor protein, thereby bypassing cell cycle checkpoints and inhibiting apoptosis (NCI Drug Dictionary). The TCR is engineered to recognize a specific E6 peptide, most commonly the E6 29-38 epitope, when presented by the Human Leukocyte Antigen (HLA)-A*02:01 molecule on the surface of tumor cells (Doran et al., 2019, JCO). When expressed in a patient's T-cells (TCR-T therapy), this receptor enables the immune cells to specifically identify and lyse HPV-16-positive cancer cells, such as those in cervical, oropharyngeal, and anal carcinomas (ClinicalTrials.gov, NCT04558411). Because E6 is a viral protein not expressed in healthy human tissues, this TCR-based approach offers high tumor specificity and a favorable safety profile regarding on-target, off-tumor toxicity. Clinical development of these TCRs involves monitoring for cytokine release syndrome and potential off-target cross-reactivity with self-peptides.

Other names

HPV16 E6-specific TCRE6-specific T-cell receptorHPV-16 E6 TCRE6 TCR

Engineered T-cells expressing the TCR recognize the HPV-16 E6 peptide (specifically the E6 29-38 epitope) presented by HLA-A*02:01 on the surface of tumor cells, triggering T-cell activation and cytotoxic lysis of the target cells (Doran et al., 2019, JCO; Draper et al., 2015, Clin Cancer Res).