Tumor-associated plasma membrane antigens and immune receptors

Tumor-associated plasma membrane antigens and immune receptors represent a broad class of cell surface proteins that are either uniquely expressed or significantly overexpressed on malignant cells, or involved in the regulation of the immune system's response to cancer (National Cancer Institute, 2023). These molecules include classic tumor markers like HER2 and CD20, as well as immune checkpoint receptors such as PD-1 and CTLA-4 (Nature Reviews Cancer, 2021). Biologically, they facilitate essential processes including signal transduction, cell-cell adhesion, and evasion of immune surveillance, which are often hijacked by cancer cells to promote growth and metastasis (PubMed, 2022). In clinical practice, these proteins serve as the primary targets for a wide range of therapeutic modalities, including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies (NIH, 2023). By binding to these targets, drugs can directly inhibit proliferative signals, flag cells for destruction by the immune system, or release the brakes on T-cells to enhance anti-tumor immunity (StatPearls, 2023). However, the therapeutic use of these targets is often complicated by off-tumor effects on healthy tissues expressing lower levels of the antigen and the development of complex resistance mechanisms (Journal of Clinical Oncology, 2022).

Other names

Tumor-associated antigensTAATumor-specific antigensTSAImmune checkpoint receptorsCancer cell surface markersCancer-testis antigensCTASurface-expressed tumor antigens

Therapeutic agents targeting this group act through various mechanisms, including the blockade of inhibitory immune checkpoints to enhance T-cell activity, direct inhibition of growth factor signaling, and the induction of antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) (Nature Reviews Drug Discovery, 2020).