Patient-specific tumor neoantigen (Neoantigen) (Neoantigen)

Patient-specific tumor neoantigens are unique proteins arising from somatic mutations within a patient's tumor genome that are not found in healthy tissues [8, 10]. When these neoantigens are derived from cancer-initiating cells (CICs), also known as cancer stem cells, they represent a high-priority therapeutic target because CICs are often resistant to conventional chemotherapy and are responsible for tumor recurrence and metastasis [7, 14]. These antigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by the host's T cells as foreign [1, 10]. Therapeutic strategies, such as personalized mRNA vaccines (e.g., mRNA-4157) or adoptive cell therapies, aim to prime the immune system to specifically recognize and eliminate these mutation-bearing cells [5, 11]. Because neoantigens are absent from the normal proteome, they offer a high degree of selectivity and a reduced risk of off-target autoimmunity compared to tumor-associated antigens [12]. However, the high degree of intratumoral heterogeneity and the ability of tumors to downregulate MHC expression remain significant challenges in effectively targeting these antigens [14, 15].

Other names

Tumor-specific antigen (TSA)NeoepitopeCancer stem cell neoantigenCIC-specific antigenSomatic mutation-derived antigenPrivate neoantigen

Induction of a patient-specific immune response by presenting tumor-specific mutated peptides via MHC molecules to activate cytotoxic T lymphocytes (CD8+) and helper T cells (CD4+), specifically targeting the self-renewing cancer-initiating cell population to prevent recurrence [1, 7, 10].