Cell surface antigens on cancer cells (TAA/TSA)

Cell surface antigens on cancer cells are a diverse group of molecules, including proteins, glycoproteins, and glycolipids, expressed on the plasma membrane of malignant cells (Vigneron, 2015, BioMed Research International). These antigens are broadly categorized into tumor-specific antigens (TSAs), which are unique to cancer cells, and tumor-associated antigens (TAAs), which are overexpressed or aberrantly expressed compared to normal tissues (NCI Dictionary). They serve as critical docking sites for targeted therapies, including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cells (Scott et al., 2012, Nature Reviews Cancer). By targeting these surface markers, therapies can selectively deliver cytotoxic payloads or induce immune-mediated destruction of the tumor via mechanisms like antibody-dependent cellular cytotoxicity (Labrijn et al., 2019, Nature Reviews Drug Discovery). However, the effectiveness of targeting these antigens is often limited by heterogeneous expression within the tumor and the potential for on-target, off-tumor toxicity if the antigen is also present on healthy cells (Srivastava & Riddell, 2018, Trends in Immunology).

Other names

Tumor-associated antigensTumor-specific antigensCancer cell surface markersNeoantigensOncoantigensTumor surface proteins

Therapeutic agents bind to these antigens to trigger immune-mediated cell death such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), inhibit oncogenic signaling pathways, or deliver cytotoxic drugs directly to the tumor cell (Labrijn et al., 2019, Nature Reviews Drug Discovery).