Clinical

Although there are many advances in the treatment of cancer, today there remains a tremendous unmet medical need in oncology, particularly with respect to disease that has spread and is no longer responsive to treatment. Cancer remains the second-leading cause of death in the developed world.

There is considerable pre-clinical evidence suggesting that targeting IL-1α might serve as an effective anti-cancer agent. Decades of observations and numerous research endeavors have shown that IL-1 plays a crucial role in inflammatory processes that are involved in tumor growth and metastasis.

Indeed, for a century it has been noted that infiltrating white blood cells are often present in tumors. This was a paradoxical observation, since the white blood cells of the immune system were considered to be the body’s main defensive mechanism against disease. It is now a common understanding among pathologists that significant white blood cell infiltration into tumors is associated with aggressive disease and poor survival. With great strides in understanding tumor biology and inflammation, it is now well understood how white blood cells can actually promote—rather than defend against—tumor growth.

White blood cells can and do play a key role in the development of a malignant phenotype. The role of white blood cells in creating a permissive environment for tumor growth and metastasis has been well elucidated, including the role of inflammatory cells in promoting tumor neo-angiogenesis, tissue-matrix remodeling and tumor invasiveness.

Various factors are produced by the growing (and necrotic) tumor to recruit white blood cells. In turn, infiltrating white blood cells produce factors that potentiate tumor growth. It is a vicious cycle that supports growth and distribution of tumors.

IL-1α has emerged as a prevalent—perhaps even universal—actor, with a potentially crucial role in the cascade of events that promote tumor growth. It is well documented in the medical literature that both white blood cells and tumor cells can produce IL-1α.

IL-1α is one of the most important regulators of inflammation. Its list of roles includes regulating: angiogenesis; tissue matrix remodeling; vascular adhesive properties; peripheral blood mononuclear cell (PBMC) proliferation; as well as induction of other inflammatory cytokines—activities which malignant cells must exploit in order to achieve growth and metastasis.

Numerous anti-cancer agents have been developed that modulate various aspects of tumor-promoting inflammatory processes. We are all well aware of these treatments and their success, which include anti-VEGF monoclonal antibody therapies; thalidomide-related drugs; protein kinase inhibitors; and cytotoxic chemotherapy.

However, ultimately many malignancies are refractory to these approaches and continued improvement is necessary. By targeting IL-1α with a monoclonal antibody, we believe that it is possible to simultaneously undermine a number of crucial pathways—specifically associated with chronic, pathological inflammatory responses—that support tumor growth.