Oral mucositis is a serious and often dose-limiting side effect of cancer chemotherapy and radiation therapy. According to a 2008 report from the National Comprehensive Cancer Network, mucositis has "emerged as the most significant adverse symptom of cancer therapy reported by patients." Mucositis is associated with severe pain and risk of infection. Patients require systemic narcotics and the insertion of a feeding tube to provide nutrition. Most significantly, when mucositis develops, the dose and frequency of cancer treatment is often reduced, leading to a significant decrease in both short-term efficacy and long-term disease-free survival.
Mucositis is initiated by direct chemical or radiation damage to the DNA of the cells lining the oral mucosa with generation of reactive oxygen species and apoptosis of epithelial cells. An inflammatory cytokine cascade is induced that centers on TNF, leading to further tissue damage. Ulcers are formed with a corresponding loss in mucosal integrity and infection. The tissue ultimately heals after the cessation of chemo or radiation therapy, but may retain a heightened sensitivity, with an increase in the incidence and severity of mucositis in subsequent cycles of cancer treatment.
We are developing a polyclonal anti-TNF antibody therapeutic to block the inflammatory cascade that is central to the development and worsening of oral mucositis.