Tumor-associated antigens and stress-induced ligands

Tumor cells expressing tumor-associated antigens (TAAs) and stress-induced ligands represent a complex therapeutic target defined by the presence of specific surface markers that distinguish malignant cells from healthy tissue. TAAs, such as HER2, CEA, or MAGE, are proteins that are either uniquely expressed by tumors or significantly overexpressed compared to normal cells (Abbott & Mellins, 2004). Stress-induced ligands, including MICA, MICB, and the ULBP family, are upregulated on the cell surface in response to genomic instability, oxidative stress, or malignant transformation (Duan et al., 2019). These molecules act as ligands for the NKG2D receptor found on Natural Killer (NK) cells and certain T cell subsets, triggering an innate and adaptive immune attack against the tumor (Zingoni et al., 2018). Therapeutic interventions, such as NKG2D-based CAR-T cells (e.g., CYAD-01) and bispecific antibodies, are designed to exploit these markers to direct cytotoxic activity specifically toward the cancer cells (Celyad Oncology). However, tumors often employ evasion strategies, such as the proteolytic shedding of stress ligands to create soluble decoys that inhibit immune cell function (Zingoni et al., 2018).

Other names

NKG2D ligandsCancer-associated antigensStress-induced moleculesTAAsMHC class I-related chain A/BUL16-binding proteins

Immune-mediated cytotoxicity via the engagement of tumor-associated antigens or stress-induced ligands by engineered T cells, NK cells, or multispecific antibodies, leading to the release of perforins and granzymes (Duan et al., 2019).