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Human papillomavirus type 18 E7 protein peptide presented by Human leukocyte antigen DRB1*09:01 (HPV18 E7/HLA-DRB1*09:01)

Target
HPV18 E7/HLA-DRB1*09:01
Molecular classification
Peptide-MHC class II complex, Antigen, Viral oncoprotein derivative
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Overview

The HPV18 E7 peptide presented by HLA-DRB1*09:01 is a specific peptide-major histocompatibility complex (pMHC) class II target used in the development of cancer immunotherapies. Human Papillomavirus type 18 (HPV18) is a high-risk viral pathogen and a primary causative agent of cervical cancer and other anogenital and oropharyngeal malignancies (Walboomers et al., 1999, PMID: 10482517). The E7 oncoprotein is a key driver of viral oncogenesis, primarily functioning by binding to and degrading the retinoblastoma (Rb) tumor suppressor protein, which leads to uncontrolled cell cycle progression (Munger et al., 1989, PMID: 2544664). HLA-DRB1*09:01 is a specific human leukocyte antigen class II allele that is particularly prevalent in East Asian populations (Gonzalez-Galarza et al., 2020, PMID: 31733060). When E7-derived peptides are processed and presented by HLA-DRB1*09:01 on the surface of tumor cells or antigen-presenting cells, they can be recognized by CD4+ T-cell receptors (TCRs). This recognition is being leveraged in the design of adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T), and therapeutic vaccines aimed at inducing a robust, targeted immune response against HPV18-positive tumors (Jin et al., 2018, PMID: 30012516). Because E7 is a viral protein not expressed in healthy human tissues, it represents a highly specific target with a low risk of on-target, off-tumor toxicity.

Other names
HPV18 E7:HLA-DRB1*09:01 complexHPV18 E7 epitopeHLA-DRB1*09:01-restricted HPV18 E7 peptideHPV18 E7 (44-58) peptide presented by HLA-DRB1*09:01
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Mechanism of action

T-cell receptor (TCR) binding to the peptide-MHC complex, triggering CD4+ T-cell activation and subsequent anti-tumor immune responses.

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Biological functions

Antigen presentationT-cell activationImmune responseCD4+ T-cell recognition
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Disease associations

Cervical cancerOropharyngeal cancerAnal cancerInfectionHPV-associated malignancy
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Safety considerations

Off-target toxicity due to TCR cross-reactivity with self-peptidesCytokine release syndrome (CRS)Immune evasion via HLA downregulation in tumor cellsNeurotoxicity (ICANS) in adoptive cell therapies
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Interacting drugs

TCR-engineered T-cell therapy (experimental)

2 more in the full profile.

07

Biomarkers

HLA-DRB1*09:01 genotypeHPV18 E7 expressionHPV18 DNA/RNA detectionE7-specific CD4+ T-cell frequency

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