Histone-associated DNA (TNT target)

Histone-associated DNA in necrotic tumor regions is a specialized therapeutic target utilized in Tumor Necrosis Therapy (TNT). While DNA is normally sequestered within the nucleus of healthy cells, the compromised membrane integrity of necrotic cells in solid tumors exposes DNA-histone complexes (nucleosomes) to the extracellular environment (Chen et al., 1989, Cancer Res). Monoclonal antibodies, such as TNT-1 or NHS-76, are engineered to bind these insoluble intracellular antigens that become accessible only in dead or dying tumor cells (Sharifi et al., 2001, Hybridoma). This targeting strategy allows for the concentrated delivery of radioisotopes, like Iodine-131, or immunomodulatory cytokines, like Interleukin-12, to the center of the tumor mass (Fallahi et al., 2013, J Cancer Res Ther). Because necrosis is a common feature of most large solid tumors, this target offers a broad-spectrum approach that is less dependent on the heterogeneous expression of cell-surface antigens.

Other names

Histone-associated exposed DNA in necrotic tumor regionsNecrotic DNADNA-histone complexNucleosomeExposed DNA in necrotic coreTumor Necrosis Therapy target

Targeted delivery of therapeutic payloads (radioisotopes or cytokines) to the necrotic core of tumors by binding to exposed DNA-histone complexes (Street et al., 2006, Curr Oncol Rep).