Deimmunized TLR5 Agonist for Anticancer Therapy

ABSTRACT: Radiotherapy is widely used to treat various types of cancer; however, its effectiveness is frequently limited by severe adverse effects resulting from radiation-induced damage to normal tissues in the tumor environment. Due to the scale of thisproblem and the current lack of safe and effective countermeasures against radiation toxicity, development of such agents is of broad significance for human health and presents an outstanding business opportunity. The new experimental drug CBLB502 is an agonist of mammalian Toll-like receptor 5 (TLR5) derived from its natural ligand, bacterial flagellin. CBLB502 is a powerful radioprotectant that was shown to selectively protect normal tissues, but not tumors, from radiation damage. In a recent study, CBLB502 effectively suppressed radiation-induced oral mucositis in a mouse model of head and neck cancer radiotherapy, while not reducing the antitumor efficacy of the radiation treatment. In fact, CBLB502 had a direct growth-suppressive effect on TLR5-express