Stressed, virally infected, or tumor cells expressing stress-induced molecules and tumor-associated antigens

This target designation describes a broad category of compromised host cells—specifically those undergoing malignant transformation, viral infection, or severe physiological stress—rather than a single molecular entity [1]. These cells are characterized by the surface display of 'danger signals' such as stress-induced NKG2D ligands (e.g., MICA, MICB, and ULBPs) and various tumor-associated antigens (TAAs) like HER2 or CD19 [2][3]. In the context of viral infection, these cells may also present non-self viral proteins via MHC Class I molecules or display viral glycoproteins on their plasma membrane [4]. Therapeutic strategies targeting these cells, such as CAR-T/NK cell therapies and bispecific antibodies, aim to exploit these molecular signatures to induce selective immune-mediated lysis [5]. However, the clinical application is challenged by the potential for 'on-target, off-tumor' toxicity if these markers are expressed on healthy tissues, as well as the ability of tumor cells to downregulate these antigens to evade immune detection [6]. Citations: [1] Groh V, et al. (1998). Science. 279(5357):1737-40. [2] Raulet DH, et al. (2013). Nat Rev Immunol. 13(10):705-17. [3] Abbas AK, et al. (2021). Cellular and Molecular Immunology. [4] Lanier LL. (2008). Nat Immunol. 9(5):495-502. [5] Shimasaki N, et al. (2020). Nat Rev Drug Discov. 19(3):200-18. [6] Sun S, et al. (2020). Signal Transduct Target Ther. 5(1):228.

Other names

Target cellsPathological cellsTransformed cellsInfected host cellsNKG2D ligand-expressing cellsAntigen-bearing cells

Targeted cell lysis via immune effector recruitment (e.g., NK cells, T cells) or antibody-dependent cellular cytotoxicity (ADCC) triggered by the recognition of stress ligands or tumor antigens.