Target intelligence / Profile preview

Peptide–HLA-A*24:02 complex (pHLA-A*24:02)

Target
pHLA-A*24:02
Molecular classification
MHC Class I complex, Antigen-presenting molecule, Receptor-ligand complex
01

Overview

Peptide–HLA-A*24:02 complexes are major histocompatibility complex (MHC) class I molecules that present short intracellularly derived peptides on the cell surface for recognition by CD8+ T cells [Frontiers in Immunology, 2021]. These complexes play a fundamental role in immune surveillance by displaying fragments of cellular proteins, including those derived from viruses or mutated/aberrantly expressed tumor antigens [NIH, 2024]. HLA-A*24:02 is a highly prevalent allele in East Asian populations, particularly in Japanese and Chinese cohorts, making it a significant target for precision oncology in these regions [Immunology, 2020]. In cancer, these complexes present tumor-associated antigens such as NY-ESO-1, MAGE-A4, and WT1, which can be targeted by TCR-engineered T cells (TCR-T) or TCR-like antibodies [Takara Bio; ClinicalTrials.gov]. The therapeutic goal is to trigger a potent and specific cytotoxic T-cell response against tumor cells while sparing healthy tissues [Oncotarget, 2017]. However, a major challenge is the potential for off-target cross-reactivity, where the therapeutic agent recognizes similar peptides presented on normal cells, potentially leading to severe toxicity [Kavraki Lab; NIH]. Clinical development of drugs targeting these complexes, such as TBI-1301 and TAEST16001, has shown promise in treating various solid tumors [Annals of Oncology, 2019; ResearchGate, 2023].

Other names
HLA-A*24:02-restricted peptide complexpMHC-A*24:02HLA-A24-peptide complexPeptide-MHC Class I complex (HLA-A*24:02)HLA-A*24:02-antigen complex
02

Mechanism of action

Recognition by engineered or endogenous T-cell receptors (TCRs) on CD8+ T cells, triggering cytotoxic activity and cytokine release to eliminate the target cell [Frontiers in Immunology, 2021; NIH, 2024].

03

Biological functions

Antigen presentationImmune surveillanceT-cell activationCD8+ T-cell recognition
04

Disease associations

CancerInfectionAutoimmune disease
05

Safety considerations

Off-target cross-reactivity with self-peptides [Kavraki Lab]On-target off-tumor toxicity [NIH]Cytokine release syndrome (CRS) [Annals of Oncology, 2019]Neurotoxicity [NIH]
06

Interacting drugs

TBI-1301 (NY-ESO-1 TCR-T)

6 more in the full profile.

07

Biomarkers

HLA-A*24:02 genotype [NIH]Tumor-associated antigen expression (e.g., NY-ESO-1, MAGE-A4, AFP) [Takara Bio]pHLA surface density [Frontiers in Immunology, 2021]

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