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T cell receptor specific for Human Papillomavirus type 16 E7 (11-19) presented by HLA-A*02:01 (HPV16 E7 TCR) (HPV16 E7 TCR)

Target
HPV16 E7 TCR
Molecular classification
T cell receptor, Receptor
01

Overview

The T cell receptor (TCR) specific for Human Papillomavirus type 16 (HPV16) E7 (11-19) presented by HLA-A*02:01 is a specialized immune receptor utilized in adoptive cell transfer therapies for the treatment of HPV-associated malignancies. HPV16 is a high-risk virus responsible for the majority of cervical cancers and a significant proportion of oropharyngeal, anal, and vulvar cancers (Draper et al., 2015, Clin Cancer Res). The E7 protein is a viral oncoprotein essential for malignant transformation and is constitutively expressed in HPV-infected tumor cells, making it an ideal, tumor-specific target. This TCR is engineered to recognize the E7 peptide fragment (amino acids 11-19, YMLDLQPET) when presented by the HLA-A*02:01 MHC class I molecule (Nagarsheth et al., 2021, JCI Insight). Upon recognition of the peptide-MHC complex, T cells expressing this TCR undergo activation, leading to the secretion of cytotoxic molecules and pro-inflammatory cytokines that mediate tumor cell lysis. Clinical trials have demonstrated that infusion of these TCR-engineered T cells can induce objective clinical responses and durable regressions in patients with metastatic HPV16-positive cancers (Doran et al., 2019, J Clin Oncol). Key therapeutic challenges include the requirement for patient HLA-A*02:01 matching and the potential for tumor escape through HLA downregulation. Safety considerations primarily involve cytokine release syndrome and the theoretical risk of cross-reactivity with human self-peptides (Nagarsheth et al., 2021, JCI Insight).

Other names
HPV16 E7-specific TCRE7 TCRYMLDLQPET-specific TCRHLA-A*02:01-restricted HPV16 E7 TCR
02

Mechanism of action

The TCR-engineered T cells recognize the HPV16 E7 peptide (11-19) presented by HLA-A*02:01 on tumor cells, triggering T cell activation, cytokine release, and direct cytotoxic killing of the target cell.

03

Biological functions

Immune responseAntigen recognitionT cell activationCytolysis
04

Disease associations

CancerInfectionCervical cancerOropharyngeal cancerAnal cancer
05

Safety considerations

Cytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)On-target off-tumor toxicity due to cross-reactivityHLA downregulation or loss in tumor cells
06

Interacting drugs

HPV-16 E7-specific TCR-transduced T cells

1 more in the full profile.

07

Biomarkers

HLA-A*02:01 positivityHPV16 E7 expressionHPV16 DNA/RNA presence

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