Glioma-associated antigens (GAA) (GAA)

Glioma-associated antigens (GAAs) are a diverse group of proteins and glycoproteins that are preferentially or uniquely expressed on the surface of glioma cells, particularly in high-grade glioblastomas. These antigens, which include Epidermal Growth Factor Receptor variant III (EGFRvIII), Interleukin-13 receptor alpha 2 (IL-13Rα2), and Human Epidermal Growth Factor Receptor 2 (HER2), serve as critical markers for distinguishing malignant cells from healthy neural tissue. Biologically, these molecules often function as receptors or signaling mediators that drive tumor proliferation, invasion, and resistance to standard therapies. Because of their accessible extracellular domains, GAAs are the primary focus for the development of targeted therapies such as chimeric antigen receptor (CAR) T-cells, monoclonal antibodies, and peptide-based vaccines. However, the clinical utility of targeting GAAs is frequently challenged by intratumoral heterogeneity and the phenomenon of antigen escape, where the tumor evolves to lose expression of the targeted antigen following treatment. Sources: [1] O'Rourke et al. (2017) Sci Transl Med, 9(399); [2] Brown et al. (2016) N Engl J Med, 375(26); [3] Wen et al. (2019) Clin Cancer Res, 25(19); [4] Sampson et al. (2017) Semin Immunol, 34.

Other names

Glioma-associated tumor cell surface antigensGAAGlioma surface antigensGlioblastoma-associated antigens

Therapeutic agents targeting these antigens work by either directly inhibiting the signaling pathways of the surface receptors or by utilizing the antigens as docking sites for immune-mediated destruction, such as through CAR T-cell activation or vaccine-induced T-cell responses [1, 2, 3].