Neoantigen-major histocompatibility complex (Neoantigen-MHC) (NeoAg-MHC)

Patient-specific tumor antigens, or neoantigens, are novel peptides resulting from non-synonymous somatic mutations unique to an individual's tumor (Nature, 2017). These peptides are processed and presented on the surface of cancer cells by Major Histocompatibility Complex (MHC) molecules, forming a complex that serves as a primary target for the adaptive immune system (Science, 2015). Unlike shared tumor-associated antigens, neoantigens are absent from normal tissues, which significantly reduces the risk of central tolerance and off-target autoimmune effects (NEJM, 2014). Autologous tumor-infiltrating lymphocytes (TILs) are naturally occurring immune cells that have migrated into the tumor to recognize these specific peptide-MHC complexes (Nature Medicine, 2022). Therapeutic interventions, such as TIL therapy (e.g., Lifileucel) and personalized neoantigen vaccines, aim to expand or prime the patient's T-cell repertoire to specifically attack cells displaying these unique signatures (Cell, 2020). This target represents a cornerstone of precision oncology, leveraging the high specificity of the immune system to achieve durable clinical responses in solid tumors.

Other names

Tumor-specific neoantigensNeoepitopesPatient-specific tumor antigenspMHC complexesTumor-specific antigens (TSA)Mutation-derived antigens

Binding of T-cell receptors (TCRs) on autologous lymphocytes to the peptide-MHC complex triggers cytotoxic T-lymphocyte activation and subsequent lysis of the tumor cell.