Target intelligence / Profile preview

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

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

The Human papillomavirus type 16 E7-specific T cell receptor (HPV16 E7 TCR) is a specialized immune receptor utilized in adoptive T-cell therapies to target cancers driven by high-risk HPV16 infection. The E7 oncoprotein is a critical driver of viral oncogenesis, as it binds and inactivates the retinoblastoma (Rb) tumor suppressor protein, leading to uncontrolled cell cycle progression (PubMed: 26351325). Because E7 is a foreign viral protein constitutively expressed in malignant cells but absent in healthy human tissue, it represents an ideal target for immunotherapy. TCR-T cell therapies involve engineering a patient's CD8+ T cells to express a high-affinity TCR specific for E7 peptides, most notably the E7:11-19 epitope presented by HLA-A*02:01 (PubMed: 30104351). Once infused, these engineered T cells recognize the peptide-MHC complex on tumor surfaces, triggering a cytotoxic immune response that includes the release of perforin, granzymes, and pro-inflammatory cytokines to induce apoptosis in the target cancer cells (NIH: NCT02858310). This approach offers a precision medicine strategy for patients with refractory HPV-associated squamous cell carcinomas.

Other names
HPV16 E7-specific TCRE7-targeted T cell receptorHPV-16 E7 TCRE7-reactive T cell receptor
02

Mechanism of action

Adoptive cell transfer of T cells engineered to express a high-affinity T cell receptor (TCR) that recognizes HPV16 E7 oncoprotein peptides presented by specific Human Leukocyte Antigen (HLA) molecules, leading to targeted lysis of HPV-infected malignant cells.

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Biological functions

Immune responseAntigen recognitionCell-mediated cytotoxicitySignal transduction
04

Disease associations

CancerInfectionCervical cancerHead and neck squamous cell carcinomaAnal cancerVulvar cancer
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Safety considerations

Cytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)Potential cross-reactivity with self-antigens (molecular mimicry)On-target off-tumor toxicity (low risk due to viral origin of the antigen)
06

Interacting drugs

KITE-439

3 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeHPV16 E7 mRNA expressionHPV16 E7 protein expressionCirculating tumor HPV16 DNA (ctDNA)

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