Tenascin-C fibronectin type III-A1 domain (TNC-A1)

Tenascin-C (TNC) is a large, hexameric extracellular matrix glycoprotein that plays a pivotal role in tissue remodeling and development (Frontiers in Immunology, https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.591266/full). The FNIII-A1 domain is one of the alternatively spliced fibronectin type III-like repeats specifically included in the "large" isoforms of the protein, which are virtually absent in healthy adult tissues but highly upregulated in pathological states (NIH, https://pubmed.ncbi.nlm.nih.gov/16707621/). These isoforms are prominently expressed in the stroma of various solid tumors, such as glioblastoma, lung, and breast cancers, as well as in chronic inflammatory conditions like rheumatoid arthritis and inflammatory bowel disease (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622652/; Google APIs, https://patents.google.com/patent/WO2017097990A1/en). The FNIII-A1 domain serves as a highly specific marker for these diseases, making it an attractive target for site-specific delivery of therapeutic agents. The human monoclonal antibody F16 specifically binds to this domain and has been utilized to deliver payloads such as interleukin-2 (Teleukin) or radioisotopes (e.g., 131I) directly to the disease site (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622652/). This targeted approach aims to enhance therapeutic efficacy while reducing systemic toxicity by exploiting the restricted expression pattern of the FNIII-A1-containing TNC isoforms. Beyond its role as a docking site, the domain contributes to the matricellular functions of TNC, influencing cell adhesion, migration, and immune modulation within the tumor microenvironment (Frontiers in Oncology, https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.609549/full).

Other names

FNIII-A1 domain of Tenascin-CTenascin-C domain A1TNC FNIII-A1Alternatively spliced domain A1 of Tenascin-C

Targeted delivery of bioactive molecules such as cytokines or radioisotopes to the disease-associated extracellular matrix