Patient-specific human leukocyte antigen (HLA) molecule presenting tumor neoantigen peptide (HLA-neoantigen complex)

Patient-specific HLA molecules presenting tumor neoantigen peptides are unique molecular complexes formed when mutated proteins within a cancer cell are processed and displayed on the cell surface by Human Leukocyte Antigen (HLA) proteins (Nature Reviews Cancer, 2021). These complexes are highly specific to the individual patient because they depend on both the patient's unique HLA genotype and the specific somatic mutations present in their tumor (NEJM, 2017). Their primary biological function is to act as "red flags" for the adaptive immune system, allowing CD8+ and CD4+ T cells to distinguish malignant cells from healthy ones through T-cell receptor (TCR) recognition (Science, 2019). In the context of disease, the presence of these neoantigens is often correlated with better responses to checkpoint inhibitors and forms the basis for next-generation personalized immunotherapies (Nature, 2023). Therapeutic strategies targeting these complexes include personalized mRNA or DNA vaccines, such as mRNA-4157 and Autogene cevumeran, which prime the immune system to recognize the neoepitopes, and TCR-T cell therapies, which use engineered receptors to bind the HLA-peptide complex directly (Lancet, 2023). A significant challenge in targeting these molecules is the phenomenon of "immune escape," where tumors downregulate HLA expression or lose specific alleles to avoid detection (Science, 2017).

Other names

MHC-neoantigen complexTumor-specific antigen (TSA) complexNeoepitope-HLA complexpHLA (peptide-HLA) complex

Vaccine-mediated induction of neoantigen-specific T-cell responses or direct targeting via engineered T-cell receptors (TCRs) that recognize the specific peptide-HLA complex on the tumor cell surface.