Neoantigen peptide-HLA complex (NeoAg-HLA)

The Neoantigen peptide-HLA complex is a pivotal target in the field of precision oncology, representing a unique molecular signature on the surface of cancer cells. It is formed when somatic mutations in the tumor genome produce novel protein fragments, known as neoantigens, which are then processed and presented by the Human Leukocyte Antigen (HLA) system (Schumacher & Schreiber, Science, 2015). Because these neoantigens are absent from the normal human proteome, they allow the immune system to bypass central tolerance and mount a highly specific anti-tumor response (Blass & Ott, Nature Reviews Clinical Oncology, 2021). T-cell receptors (TCRs) on the surface of CD8+ and CD4+ T cells recognize these complexes with high affinity, leading to the activation of cytotoxic pathways and the subsequent lysis of the tumor cell. Current therapeutic interventions targeting these complexes include personalized mRNA or peptide vaccines, such as mRNA-4157, and adoptive cell therapies using TCR-engineered T cells (Weber et al., The Lancet, 2024). However, the clinical success of these therapies is often challenged by tumor-mediated immune evasion, such as the downregulation of HLA molecules or the loss of the specific neoantigen (Sahin & Türeci, Science, 2018). Furthermore, ensuring that engineered TCRs do not cross-react with similar wild-type peptides in healthy tissues is a critical safety consideration in drug development (Rosenberg & Restifo, Science, 2015).

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexNeoantigen-pMHCMutated peptide-HLA complexTCR-pMHC complex

Induction of antigen-specific T-cell responses through the recognition of tumor-specific mutated peptides presented by HLA molecules, leading to targeted cell lysis (Rosenberg & Restifo, Science, 2015).