Tumor-associated antigens and tumor-specific antigens (TAA/TSA)

Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) represent a diverse class of molecules expressed by malignant cells that serve as the primary targets for cancer immunotherapy (NCI Dictionary, 2024). TAAs are typically normal host proteins that are overexpressed, such as HER2, or expressed in immunologically privileged sites, such as cancer-testis antigens like NY-ESO-1. In contrast, TSAs, often referred to as neoantigens, are entirely novel sequences resulting from somatic mutations, viral infections, or alternative splicing unique to the patient's tumor (Nature Reviews Cancer, 2021). These antigens are processed and presented on the cell surface via Major Histocompatibility Complex (MHC) molecules, where they can be recognized by T-cell receptors. Therapeutic strategies leveraging these targets include personalized mRNA vaccines, which encode patient-specific neoantigens to prime the immune system, and adoptive cell therapies like CAR-T cells. While TSAs offer high specificity and reduced risk of autoimmunity, the inherent heterogeneity of antigen expression within a tumor remains a significant challenge for achieving complete therapeutic efficacy (Science, 2019).

Other names

Tumor antigensNeoantigensCancer-testis antigensOncofetal antigensTumor-specific neoantigensMutated self-antigens

Drugs targeting these antigens function by enhancing the immune system's ability to identify and destroy malignant cells. This is achieved through active immunization (vaccines), where the patient's immune system is primed to recognize specific TAA/TSA sequences, or through passive immunization (monoclonal antibodies and adoptive cell transfer), where pre-formed immune components are introduced to target these antigens directly (Nature Reviews Immunology, 2020; NCI, 2023).