HLA class I-presented tumor-associated antigens (HLA-I TAAs) (HLA-I TAAs)

HLA class I-presented tumor antigens are short peptide fragments, typically 8-11 amino acids in length, derived from intracellular proteins and displayed on the surface of hepatocellular carcinoma (HCC) cells by Human Leukocyte Antigen (HLA) class I molecules [Löffler et al., Nature Communications, 2019]. These peptide-HLA (pHLA) complexes are essential for the immune system to distinguish malignant cells from healthy ones, as they are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes [PubMed: 31110243]. In the context of HCC, common targets include peptides derived from oncofetal proteins like Alpha-fetoprotein (AFP) and Glypican-3 (GPC3), as well as cancer-testis antigens such as MAGE-A3 and NY-ESO-1 [Liu et al., Molecular Therapy, 2017]. Therapeutic interventions targeting these antigens include TCR-engineered T-cell (TCR-T) therapies, such as ADP-A2AFP, which provide patients' T cells with a specific receptor to recognize the pHLA complex [NCT03132792]. Other approaches include TCR-like antibodies, such as ET1402L1, which bind pHLA complexes with antibody-like affinity [Eureka Therapeutics]. A significant challenge in targeting these antigens is the requirement for specific HLA alleles (e.g., HLA-A*02:01), which limits the eligible patient population [StatPearls: HLA System]. Furthermore, tumor cells may downregulate HLA expression or antigen processing machinery to evade immune detection, necessitating strategies to enhance antigen presentation [PubMed: 28100703]. Safety concerns primarily involve potential cross-reactivity with similar peptides presented on healthy tissues, which can lead to severe off-target toxicities [Adaptimmune].

Other names

Peptide-MHC complexespHLA complexesMHC class I-restricted tumor antigensTumor-associated peptides (TAPs)HCC-specific HLA-presented peptidesAFP-HLA-A2 complexGPC3-HLA-A2 complex

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to T-cell activation, cytokine release, and targeted tumor cell lysis [PubMed: 31110243].