Tumor-derived neoantigen (Neoantigen) (Neoantigen)

Tumor-derived neoantigens are unique proteins or peptides that arise from somatic mutations within a tumor's genome, such as single nucleotide variants, insertions, deletions, or chromosomal translocations [1, 2]. Unlike tumor-associated antigens, neoantigens are not expressed in normal tissues, making them highly specific targets for the immune system and reducing the risk of central tolerance or autoimmunity [2, 4]. These antigens are processed by the cellular machinery and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules for recognition by T-cell receptors [2]. In the context of oncology, they serve as the foundation for personalized immunotherapy, including cancer vaccines and adoptive T-cell therapies designed to prime or expand the patient's own immune response against their specific tumor profile [3, 4]. The clinical utility of neoantigens is often linked to the tumor mutational burden, where higher mutation rates generally correlate with a greater likelihood of generating immunogenic neoantigens [3]. Therapeutic agents targeting these antigens, such as mRNA-4157 and RO7198457, are currently in clinical trials to evaluate their efficacy in treating various solid tumors [3, 4].

Other names

Tumor-specific antigenTSANeoepitopeSomatic mutation-derived antigenTumor-specific neoantigen

Therapeutic strategies targeting tumor-derived neoantigens involve the identification of patient-specific mutations to create personalized vaccines or adoptive cell therapies [3, 4]. These therapies aim to induce or enhance the activation and expansion of neoantigen-specific T cells, which recognize the mutated peptides presented on the tumor cell surface via MHC molecules, leading to targeted cytotoxic destruction of the cancer cells [2, 4].