Tenascin-C Fibronectin type III-A1 splice variant (TNC-A1)

Tenascin-C is a large, hexameric extracellular matrix glycoprotein that plays a critical role in tissue remodeling, embryonic development, and wound healing [4, 8]. The FNIII-A1 splice variant refers to a specific domain included in the large isoform of Tenascin-C through alternative splicing of the fibronectin type III repeats [4, 11]. While Tenascin-C is virtually undetectable in most healthy adult tissues, the A1-containing isoforms are highly overexpressed in the stroma and neovasculature of various cancers, including glioblastoma and lung carcinoma, as well as in inflammatory conditions like atherosclerosis [1, 10]. This restricted expression pattern makes the FNIII-A1 domain an attractive therapeutic target for antibody-based delivery of cytotoxic agents, radionuclides, or cytokines [1, 7]. The human monoclonal antibody F16 specifically recognizes this domain and has been used in clinical trials as part of immunocytokines, such as F16-IL2 (Teleukin), to concentrate immune-stimulating factors at the tumor site [4, 10]. Targeting this variant allows for the selective accumulation of therapeutic payloads in the disease microenvironment while minimizing systemic toxicity [1, 13].

Other names

TNC-A1Tenascin-C A1 domainLarge isoform of Tenascin-COncofetal Tenascin-C

Targeted delivery of bioactive molecules (e.g., cytokines, radionuclides) to the tumor microenvironment or inflammatory sites by binding specifically to the A1 domain of the large Tenascin-C isoform.