Glioblastoma-associated antigen (GAA)

Glioblastoma-associated antigens (GAAs) are a heterogeneous group of proteins that are significantly overexpressed or uniquely expressed in glioblastoma multiforme (GBM) compared to healthy brain tissue. This category encompasses a wide range of molecules, including surface receptors like IL-13Rα2 and EGFRvIII, as well as intracellular proteins such as Survivin (BIRC5), TRP-2, and gp100, which are often involved in promoting tumor cell proliferation, survival, and immune evasion [19, 22]. These antigens serve as the primary targets for various immunotherapeutic strategies, including multi-peptide vaccines like ICT-107 and adoptive cell therapies such as CAR-T and TCR-T cells [1, 8, 10]. Because glioblastoma is characterized by extreme intratumoral heterogeneity, single-antigen targeting often leads to "antigen escape," where the tumor recurs by losing the targeted protein. Consequently, modern therapeutic approaches frequently target multiple GAAs simultaneously to ensure a more robust and durable clinical response [2, 26]. While GAAs offer a promising avenue for precision medicine in one of the most aggressive forms of brain cancer, therapeutic success is often limited by the immunosuppressive tumor microenvironment and the challenge of identifying targets with minimal off-target expression in the central nervous system [12, 28].

Other names

Glioma-associated antigenTumor-associated antigen (TAA)Glioblastoma-specific antigenGlioblastoma stem-like cell-associated antigen (SAA)Interleukin-13 receptor subunit alpha-2 (IL13RA2)Epidermal growth factor receptor variant III (EGFRvIII)Neuroligin-4, X-linked (NLGN4X)Protein tyrosine phosphatase receptor type Z1 (PTPRZ1)

Active immunotherapy via peptide-based or dendritic cell vaccination to stimulate cytotoxic T-lymphocyte responses; adoptive cell transfer using chimeric antigen receptor (CAR) T-cells or T-cell receptor (TCR) engineered T-cells for direct tumor lysis; targeted delivery of cytotoxic payloads via ligand-receptor binding.