IL-15: Taking an immunotherapy from bench to bedside
Cytokines are a class of proteins that regulate signaling in the immune system. Since the 1970s, scientists have worked to better understand the large and complex family of cytokine molecules, in hopes of harnessing them to more effectively combat cancer and other diseases.
IRP researchers led by Thomas Waldmann, M.D., co-discovered the cytokine IL-15 and revealed its powerful role in triggering a cascade of tumor-fighting immune system cells. The lab demonstrated that IL-15’s unique properties made it a potentially better immunotherapy than IL-2, a related protein in clinical use today.
Dr. Waldmann’s team then translated their observations from the research bench to the clinic by initiating the first clinical trials in humans using the cytokine as a cancer therapy. IL-15 is now being tested to treat patients with metastatic malignant melanoma and renal cell cancer. IL-15 has also shown promise in molecular vaccines, which could represent a major advance in treating cancer and autoimmune disorders such as AIDS.
Bamford RN, Grant AJ, Burton JD, Peters C, Kurys G, Goldman CK, Brennan J, Roessler E, Waldmann TA. (1994). The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Nat Acad Sci U S A. 91(11), 4940-4.
Waldmann TA, Lugli E, Roederer M, Perera LP, Smedley JV, Macallister RP, Goldman CK, Bryant BR, Decker JM, Fleisher TA, Lane HC, Sneller MC, Kurlander RJ, Kleiner DE, Pletcher JM, Figg WD, Yovandich JL, Creekmore SP. (2011). Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques. Blood. 117(18), 4787-95.
Waldmann TA, Conlon KC, Stewart DM, Worthy TA, Janik JE, Fleisher TA, Albert PS, Figg WD, Spencer SD, Raffeld M, Decker JR, Goldman CK, Bryant BR, Petrus MN, Creekmore SP, Morris JC. (2013). Phase 1 trial of IL-15 trans presentation blockade using humanized Mikβ1 mAb in patients with T-cell large granular lymphocytic leukemia. Blood. 121(3), 476-84.