Tumor neoantigen-Human Leukocyte Antigen complex (NeoAg-HLA) (NeoAg-HLA)

Tumor neoantigens are unique peptides resulting from non-synonymous somatic mutations occurring specifically within cancer cells (Nature Reviews Cancer, 2017). These mutant proteins are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Frontiers in Immunology, 2020). The resulting tumor neoantigen-HLA complex serves as a highly specific signal recognized by the T cell receptor (TCR) of cytotoxic T lymphocytes (Science, 2015). Because these antigens are absent from normal tissues, they represent ideal therapeutic targets with high tumor specificity and low risk of autoimmune toxicity (Journal of Hematology & Oncology, 2021). Therapeutic approaches include personalized vaccines designed to stimulate endogenous T cells and adoptive cell therapies using TCR-engineered T cells (Nature, 2019). The effectiveness of these treatments is often dependent on the patient's specific HLA genotype and the immunogenicity of the identified neoepitopes (Cell, 2017). However, challenges such as intratumoral heterogeneity and the loss of HLA expression can lead to resistance and treatment failure (Nature Medicine, 2020). Ongoing research focuses on improving neoantigen prediction algorithms and developing therapies for common driver mutations like KRAS (Cancer Discovery, 2022).

Other names

Neoepitope-HLA complexTumor-specific antigen (TSA)Mutant peptide-MHC complexNeoantigen-MHC class I complexNeoantigen-MHC class II complex

Induction of neoantigen-specific T-cell activation and expansion to mediate tumor cell lysis.