Mutant Epidermal Growth Factor Receptor-derived neoantigen peptide-HLA class I complex (Mutant EGFR neoantigen-HLA complex)

Mutant Epidermal Growth Factor Receptor (EGFR)-derived neoantigen peptides presented by specific Human Leukocyte Antigen (HLA) class I alleles represent a class of tumor-specific targets for cancer immunotherapy. These neoantigens arise from somatic mutations in the EGFR gene, such as the L858R point mutation or Exon 19 deletions, which are common drivers in non-small cell lung cancer (NSCLC) [1.1.1, 1.2.1]. When these mutated proteins are processed by the cellular proteasome, the resulting mutant peptides are loaded onto HLA class I molecules and displayed on the cell surface for recognition by CD8+ T cells [1.1.2, 1.3.5]. Because these peptides contain amino acid sequences not found in the normal proteome, they can elicit potent, tumor-specific immune responses while sparing healthy tissues [1.2.2, 1.2.5]. Therapeutic strategies targeting these complexes include personalized peptide or mRNA vaccines designed to induce de novo T-cell responses, as well as adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize specific peptide-HLA combinations [1.3.1, 1.3.2]. However, the efficacy of these treatments can be hindered by immune evasion mechanisms, such as the loss of HLA expression (HLA LOH) or the presence of an immunosuppressive tumor microenvironment [1.3.3, 1.4.1]. Clinical studies have shown that patients harboring protective HLA alleles capable of presenting these neoantigens often have better prognoses and are more likely to respond to neoantigen-directed therapies [1.1.3, 1.2.4].

Other names

EGFR neoepitopeEGFR mutation-derived neoantigenEGFR pHLA complexEGFR L858R/HLA-A*11:01 complexEGFR T790M/HLA-C*15:02 complexEGFRvIII peptide-HLA complex

Therapies targeting these complexes work by either actively immunizing the patient to induce de novo T-cell responses (vaccines) or by providing ex vivo expanded or engineered T cells (TCR-T) that specifically recognize the mutant peptide in the context of a specific HLA allele, leading to targeted destruction of tumor cells.