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

Tumor-specific neoantigen-Human Leukocyte Antigen (HLA) complexes are unique molecular targets formed when mutated proteins within a cancer cell are degraded into peptides and presented on the cell surface by HLA class I or II molecules (Schumacher & Schreiber, 2015). These neoantigens arise from somatic mutations, such as single nucleotide variants or frameshifts, and are absent from the normal human proteome, making them highly specific to the tumor (Sahin et al., 2017). The recognition of these complexes by the T-cell receptor (TCR) is a critical step in the adaptive immune system's ability to distinguish malignant cells from healthy tissue (Ott et al., 2017). In therapeutic contexts, these complexes are targeted using personalized vaccines—including mRNA, DNA, and peptide platforms—or through adoptive cell therapies like TCR-engineered T cells (Alspach et al., 2019). By priming the immune system to recognize these specific neoepitopes, these therapies aim to induce a robust, durable, and highly selective anti-tumor response. The clinical utility of these targets is currently being explored in various solid tumors, often in combination with immune checkpoint inhibitors to overcome local immunosuppression.

Other names

Tumor-specific neoantigen peptides bound to patient HLA class I and IINeoantigen-HLA complexTumor-specific neoepitopepHLA complexNeoepitope-MHC complexTumor-specific antigen (TSA)

Induction of a personalized immune response where vaccines or cell therapies enable T-cells to recognize and destroy tumor cells presenting unique mutation-derived peptides on HLA molecules (Sahin et al., 2017).