Patient-specific tumor-associated antigens (TSA) (TSA)

Patient-specific tumor-associated antigens (TSAs), commonly known as neoantigens, are unique proteins or peptides resulting from somatic mutations in a patient's tumor that are not present in normal tissues (Schumacher & Schreiber, Science 2015). 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 (Blass & Ott, Nature Reviews Clinical Oncology 2021). Because they are entirely foreign to the immune system, they are highly immunogenic and serve as ideal targets for personalized immunotherapy, minimizing the risk of off-target toxicity to healthy organs. Therapeutic interventions targeting these antigens include personalized mRNA vaccines, such as mRNA-4157, and adoptive cell therapies like Lifileucel, which utilize the patient's own immune cells to recognize these specific markers (Moderna/Merck, 2023; FDA, 2024). The clinical efficacy of targeting these antigens often depends on the tumor's mutational burden and the diversity of the neoantigen landscape. However, the high degree of inter-patient variability necessitates a bespoke approach to drug development, involving complex genomic sequencing and bioinformatics to identify the most potent antigenic targets for each individual. This personalized strategy aims to overcome the limitations of traditional therapies by addressing the inherent heterogeneity of human cancers.

Other names

NeoantigensTumor-specific antigensAutologous tumor antigensPersonalized tumor antigensPrivate neoantigensTumor-associated antigens (TAA)

Induction of a patient-specific cytotoxic T-lymphocyte (CTL) response against tumor cells expressing unique mutated peptides presented on MHC molecules (Schumacher & Schreiber, Science 2015).