Tumor neoantigen-HLA complex (NeoAg-HLA)

Tumor neoantigens are novel peptides derived from somatic mutations within a patient's tumor cells that are not present in normal tissues (Schumacher & Schreiber, Science, 2015). These peptides are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, forming a unique complex that can be recognized by the immune system (Hacohen et al., Cancer Immunology Research, 2013). The T-cell receptor (TCR) on cytotoxic T lymphocytes specifically binds to these neoantigen-HLA complexes, triggering a targeted immune response against the cancer cells (Ott et al., Nature, 2017). Because neoantigens are entirely tumor-specific, they represent ideal therapeutic targets with a low risk of central tolerance or autoimmune damage to healthy tissues. Current therapeutic strategies include personalized neoantigen vaccines, such as mRNA-4157/V940, which prime the immune system to recognize these markers, and adoptive T-cell therapies, where TCRs are engineered to target specific neoepitopes (Sahin et al., Nature, 2017). However, challenges remain regarding the accurate prediction of immunogenic neoantigens and the potential for tumors to escape detection through HLA downregulation or loss of heterozygosity (McGranahan et al., Cell, 2017).

Other names

Tumor-specific neoantigenNeoepitope-MHC complexMutant peptide-HLA complexPatient-specific neoantigenTSA-HLA complex

Recognition of the mutant peptide-HLA complex by the T-cell receptor (TCR) triggers the activation and proliferation of CD8+ and CD4+ T cells, leading to the targeted lysis of tumor cells expressing the specific neoantigen.