Tenascin-C (large isoform A1 domain) (TNC-A1)

Tenascin-C is a large, hexameric extracellular matrix (ECM) glycoprotein that is essential during embryogenesis but largely absent from healthy adult tissues, with the exception of specific niches like tendons and lymphoid organs [1, 4]. The large isoform of Tenascin-C is generated through alternative splicing of the fibronectin type III (FNIII) repeats, specifically including the A1 domain, and is highly overexpressed in the stroma of most solid tumors and in inflammatory conditions such as rheumatoid arthritis [2, 4]. This A1 domain serves as a highly specific marker for neo-vasculature and tissue remodeling, making it an ideal target for site-specific delivery of therapeutic agents [2, 3]. Therapeutic strategies primarily involve the use of high-affinity human monoclonal antibodies, such as F16, which can be conjugated to radioisotopes or cytokines like IL-2 and TNF-alpha to concentrate their activity at the disease site [3, 5]. By targeting the A1 domain, these therapies aim to disrupt the pro-tumorigenic microenvironment and stimulate a localized immune response while sparing healthy tissues [2, 5]. [1] UniProt Consortium. UniProtKB - P24821 (TNC_HUMAN). [2] Pedretti, M., et al. (2009). Protein Engineering, Design and Selection. [3] Schwager, K., et al. (2011). Expert Opinion on Biological Therapy. [4] Midwood, K. S., et al. (2016). Journal of Cell Science. [5] Philogen S.p.A. Pipeline: F16-IL2 and F16-TNF.

Other names

TNCCytotactinGP 150-225NeuronectinHexabrachionTenascin-C extra domain A1TNC-A1Oncofetal Tenascin-C

The primary mechanism involves the high-affinity binding of monoclonal antibodies (e.g., F16) to the A1 domain of the large Tenascin-C isoform, which is selectively expressed in the extracellular matrix of diseased tissues. This binding facilitates the localized delivery and concentration of conjugated payloads, such as cytokines (IL-2, TNF) or radionuclides, to the tumor microenvironment or inflammatory sites, thereby enhancing therapeutic efficacy while reducing systemic toxicity [2, 3, 5].