Multiple uses of tumor necrosis therapy (TNT) for the treatment and imaging of solid tumors: Preclinical considerations and progress

In an attempt to identify reagents that can elicit an effective anti-tumor immune response, we produced a panel of fusion proteins consisting of the tumor necrosis therapy (TNT) antibody and potent cytokines/chemokines. At the center of this approach is the TNT antibody, which has several important characteristics that make it an ideal delivery agent for immune modulators. These include its applicability to a wide range of human and animal cancers, its inability to bind normal tissues, its long retention time in tumors, and its ability to target necrotic regions in primary and metastatic lesions. Because of these attributes, TNT has been used to deliver radionuclides, immunostimulatory molecules, and vasopermeability agents to treat tumors. Moreover, TNT can be used with imaging to provide critical information concerning the effects of cytoreductive therapy early in the course of treatment and to demonstrate the ability of vasoactive antibody reagents to improve the uptake of drugs used for the treatment of cancer. To date over 250 patients have been treated with 131I-chTNT-3 demonstrating that all types of tumors can be targeted without significant uptake in normal tissues. TNT fusion proteins therefore have unique promise as second generation agents for the immunotherapy of solid tumors.