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

The T-cell receptor (TCR) recognizing the Human Papillomavirus-16 (HPV16) E6 peptide–MHC complex is a specialized immune receptor utilized in adoptive cell therapies for HPV-associated malignancies (National Cancer Institute, 2022). HPV16 is a high-risk virus that drives oncogenesis through the expression of the E6 oncoprotein, which facilitates the degradation of the p53 tumor suppressor (NIH, 2015). Since E6 is a viral protein constitutively expressed in cancer cells but absent in healthy tissues, it serves as a highly specific tumor antigen (AACR, 2015). Therapeutic TCRs are engineered to bind with high avidity to the E6 peptide, typically the E6 29-38 epitope, when presented by the HLA-A*02:01 molecule on the surface of tumor cells (ClinicalTrials.gov, 2024). Upon recognition, the TCR triggers T-cell activation, leading to the secretion of cytotoxic granules and pro-inflammatory cytokines that induce apoptosis in the target malignant cells (NIH, 2019). This approach is currently being evaluated in clinical trials for patients with metastatic or refractory cervical, anal, and oropharyngeal cancers, often in combination with lymphodepleting chemotherapy and interleukin-2 to enhance therapeutic efficacy and persistence (Cancer.gov, 2023).

Other names

T-cell receptor recognizing HPV16 E6 peptide–MHC complexHPV16 E6-specific TCRE6-targeting T-cell receptorHLA-A*02:01-restricted HPV16 E6 TCRE6-specific TCR

Adoptive T-cell therapy involving the genetic engineering of T cells to express a high-avidity TCR that specifically recognizes the HPV16 E6 peptide (e.g., E6 29-38) presented by the HLA-A*02:01 MHC molecule, leading to targeted lysis of HPV-positive tumor cells (National Cancer Institute, 2022).