Patient-specific tumor-associated antigen (TSA)

Patient-specific tumor-associated antigens, commonly known as neoantigens, are unique proteins produced by tumor cells as a result of somatic mutations such as single-nucleotide variants, indels, or chromosomal translocations [1][2]. Unlike shared tumor antigens, these are not expressed in normal tissues, which allows the immune system to recognize them as "non-self" and bypass central thymic tolerance [3]. These antigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they serve as specific targets for CD8+ and CD4+ T-cells [4]. Therapeutic strategies targeting these antigens include personalized mRNA, DNA, or peptide vaccines, as well as adoptive cell therapies like TCR-engineered T-cells or tumor-infiltrating lymphocytes (TILs) [5]. By focusing on mutations unique to an individual's tumor, these therapies aim to achieve high specificity and minimize off-target toxicity [6]. However, the clinical application is challenged by the need for complex bioinformatic prediction of immunogenic epitopes and the requirement for bespoke, patient-by-patient manufacturing processes [7].

Other names

NeoantigenTumor-specific antigenPrivate antigenMutation-derived antigenNeoepitope

Induction of a personalized T-cell mediated immune response against unique tumor mutations.