Patient-specific lung tumor-associated neoantigen (Neoantigen)

Patient-specific lung tumor-associated antigens, commonly known as neoantigens, are unique peptides derived from somatic mutations that occur exclusively within a patient's tumor cells [1]. These antigens are processed by the cellular machinery and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I and Class II molecules, where they are recognized by CD8+ and CD4+ T cells, respectively [2]. Because neoantigens are not present in the normal genome, they are highly immunogenic and bypass central thymic tolerance, making them ideal targets for precision immunotherapy [3]. In lung cancer, particularly non-small cell lung cancer (NSCLC), the high frequency of mutations caused by environmental factors often results in a diverse repertoire of these antigens [2]. Therapeutic strategies targeting these antigens include personalized mRNA, DNA, or peptide vaccines, as well as adoptive T-cell therapies using TCR-engineered cells [3, 4]. These interventions aim to stimulate a robust, tumor-specific immune response while sparing healthy tissues from off-target damage [1]. The clinical efficacy of these treatments is closely tied to the accurate identification of mutations and the patient's specific HLA profile [2].

Other names

NeoantigensTumor-specific antigens (TSAs)Mutation-derived antigensPatient-specific tumor antigensHLA-presented neoepitopes

Induction of a de novo T-cell response or expansion of pre-existing T-cell clones that specifically recognize mutation-derived peptides presented by HLA Class I or Class II molecules on the surface of tumor cells, leading to targeted cell lysis and cytokine production [1, 2].