Tenascin-C (isoform containing domain C) (TNC-C)

Tenascin-C (TNC) is a large, hexameric extracellular matrix (ECM) glycoprotein that plays a critical role in tissue remodeling, embryonic development, and wound healing [NIH, 2024]. While its expression is minimal in healthy adult tissues, specific "large" isoforms containing alternatively spliced fibronectin type III (FNIII) domains, such as the C-isoform (TNC-C), are highly upregulated in pathological conditions including solid tumors, atherosclerosis, and chronic inflammation [Silacci et al., 2006]. The C-isoform is characterized by the inclusion of the extra domain C, which is virtually absent in normal tissues, making it an ideal "oncofetal" antigen for targeted therapy [Pedretti et al., 2006]. Therapeutic strategies targeting TNC-C include monoclonal antibodies (e.g., G11), peptides (e.g., PL1), and CAR-T cells, which are used to deliver radionuclides, cytokines, or cytotoxic effects directly to the tumor microenvironment or atherosclerotic plaques [BMJ, 2024; Lingasamy, 2020]. Despite its promise as a biomarker and target, challenges remain regarding the efficacy of these agents in complex tumor environments and potential off-target effects in non-malignant sites of active tissue repair [NIH, 2024].

Other names

TNC-CLarge Tenascin-COncofetal Tenascin-CCytotactinHexabrachionNeuronectinGMEMJIGP 150-225Myotendinous antigen

Targeted delivery of therapeutic payloads (e.g., cytokines, radionuclides) or immune cells (CAR-T) to the tumor microenvironment or sites of tissue remodeling by binding to the alternatively spliced C domain of Tenascin-C.