Patient-specific tumor neoantigen peptide–HLA complex (pHLA complex)

The patient-specific tumor neoantigen peptide–HLA complex is a molecular assembly presented on the surface of cancer cells, consisting of a mutated peptide (neoantigen) bound to a Human Leukocyte Antigen (HLA) molecule (Sahin & Tureci, 2018). These complexes are formed when somatic mutations in the tumor genome, such as single nucleotide variants or frameshifts, result in novel protein sequences that are processed and loaded onto MHC Class I or II molecules (Ott et al., 2017). Because these neoantigens are absent from normal tissues, the resulting peptide-HLA (pHLA) complexes serve as highly specific "non-self" signals that can be recognized by the T-cell receptors (TCRs) of the host's immune system (Luksza et al., 2017). This recognition is the cornerstone of personalized cancer immunotherapies, including neoantigen vaccines like mRNA-4157 and adoptive TCR-T cell therapies, which aim to amplify the T-cell response against these unique tumor markers (Hu et al., 2021). The interaction between a TCR and its cognate neoantigen-HLA complex triggers cytotoxic activity, leading to the selective destruction of malignant cells while sparing healthy tissue. However, the therapeutic efficacy can be hindered by tumor-mediated immune evasion, such as the downregulation of HLA expression or the loss of specific HLA alleles, known as loss of heterozygosity (McGranahan & Swanton, 2017). Consequently, identifying high-affinity, immunogenic neoantigen-HLA pairs through genomic sequencing and bioinformatic prediction is a critical step in the development of individualized cancer treatments (Nielsen et al., 2020).

Other names

Neoepitope-HLA complexTumor-specific neoantigen-MHC complexMutant peptide-HLA complexPersonalized neoantigen-MHC complexpMHC complexNeoAg-HLA complex

Presentation of tumor-specific mutant peptides by HLA molecules to T-cell receptors (TCRs), inducing a targeted cytotoxic immune response against cancer cells.