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T cell receptor recognizing HPV16 E7 11–19 peptide presented by HLA-A*02:01 (HPV16 E7 TCR)

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

Overview

The T cell receptor (TCR) recognizing the HPV16 E7 11–19 peptide (YMLDLQPET) presented by HLA-A*02:01 is a high-avidity receptor utilized in adoptive T cell therapies for human papillomavirus (HPV)-associated cancers [1.2.3, 1.3.1]. HPV16 E7 is a viral oncoprotein constitutively expressed in infected cells and is essential for oncogenesis, making it an ideal tumor-specific target as it is absent in healthy tissues [1.2.5, 1.4.2]. This TCR allows engineered T cells (TCR-T) to specifically identify and eliminate cancer cells in an HLA-restricted manner [1.3.1]. Clinical trials, such as those involving the investigational product KITE-439 and NCI-developed clones, have demonstrated objective responses and significant tumor regression in patients with metastatic cervical and oropharyngeal cancers [1.1.1, 1.3.3]. However, therapeutic efficacy can be limited by tumor-mediated resistance mechanisms, such as the loss of HLA-A*02:01 expression or genetic defects in the B2M gene and antigen processing machinery [1.4.1]. Safety concerns associated with this therapy include cytokine release syndrome and neurotoxicity, which are common challenges in engineered T cell treatments [1.3.3].

Other names
HPV16 E7-specific TCRE7 TCRHPV16 E7 11-19 TCRE7 TCR-THPV16 E7-specific HLA-A*02:01-restricted T-cell receptor
02

Mechanism of action

Adoptive T cell therapy (TCR-T) involving the engineering of autologous T cells to express a specific T cell receptor that recognizes the HPV16 E7 11-19 peptide in the context of HLA-A*02:01, leading to targeted tumor cell lysis.

03

Biological functions

Immune responseAntigen recognitionCell killingT cell activationCytotoxicity
04

Disease associations

CancerInfection
05

Safety considerations

Cytokine release syndrome (CRS)Neurotoxicity (ICANS)T-cell exhaustionOff-target toxicityInsertional mutagenesis
06

Interacting drugs

KITE-439

1 more in the full profile.

07

Biomarkers

HLA-A*02:01HPV16 E7 expressionB2M (Beta-2 microglobulin) expressionInterferon-gamma (IFN-gamma) production

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