Tumor-associated antigen and Tumor-specific neoantigen (TAA/TSA)

Tumor-associated antigens (TAAs) and tumor-specific neoantigens (TSAs) are molecules expressed by cancer cells that serve as targets for the host immune system. TAAs are typically self-proteins that are overexpressed or inappropriately expressed in malignant tissues, such as HER2 or CEA, making them accessible for off-the-shelf therapies like monoclonal antibodies and CAR-T cells (National Cancer Institute, 2023). In contrast, TSAs or neoantigens arise from somatic mutations unique to an individual's tumor, providing high specificity and reducing the risk of autoimmune cross-reactivity (Nature Reviews Cancer, 2021). These antigens are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by T-cell receptors (TCRs). Modern immunotherapies, including personalized mRNA vaccines and TCR-engineered T-cells, leverage these targets to mount a precise attack against cancer (PubMed, 2022). However, challenges such as on-target off-tumor toxicity for TAAs and the logistical complexity of manufacturing personalized TSA-based treatments remain significant hurdles. The success of targeting these antigens is often dependent on the tumor mutational burden and the integrity of the patient's antigen-presentation machinery.

Other names

Tumor antigenNeoantigenCancer-testis antigenOncofetal antigenMutated self-antigenTumor-specific antigen

Therapeutic agents target these antigens to induce immune-mediated destruction of tumor cells via T-cell activation, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or direct chimeric antigen receptor (CAR) mediated lysis (Nature Reviews Drug Discovery, 2020).