Human papillomavirus type 16 E7-specific T-cell receptor (HPV16 E7 TCR)

The Human papillomavirus type 16 E7-specific T-cell receptor (HPV16 E7 TCR) is an engineered immune receptor designed to target cells expressing the E7 oncoprotein, a key driver of HPV-mediated malignancy (Draper et al., 2015, PMID: 25583380). These TCRs are typically isolated from patients with natural immune responses to HPV or generated through immunization of HLA-transgenic mice, then optimized for high affinity against the E7:11-19 peptide presented by HLA-A*02:01 (Nagarsheth et al., 2021, PMID: 33547074). In therapeutic applications, autologous T-cells are transduced with the TCR gene to create TCR-T cell therapies capable of specifically recognizing and killing HPV16-positive tumor cells. Because E7 is a viral protein not expressed in healthy human tissues, these TCRs offer a high degree of tumor specificity, reducing the risk of on-target off-tumor toxicity compared to TCRs targeting self-antigens (Doran et al., 2019, PMID: 31461376). Clinical trials have demonstrated that T-cells engineered with HPV16 E7 TCRs can induce regression of metastatic HPV-associated epithelial cancers, including cervical and oropharyngeal carcinomas (Hinrichs et al., 2017, PMID: 28783667). Ongoing research focuses on overcoming the immunosuppressive tumor microenvironment and preventing HLA downregulation, which are common mechanisms of resistance to TCR-T therapy.

Other names

HPV16 E7-targeted T-cell receptorE7-specific TCRHPV-16 E7 TCRHuman papillomavirus type 16 E7-specific TCR

Antigen-specific recognition of HPV16 E7 peptide-MHC complexes (typically E7:11-19 presented by HLA-A*02:01) leading to T-cell activation and mediated lysis of tumor cells (Nagarsheth et al., 2021, PMID: 33547074).