Biochemical and immunological characteristics of 4-1BB (CD137) receptor and ligand and potential applications in cancer therapy.

4-1BB (CD 137) is a member of the tumor necrosis factor receptor (TNFR) superfamily that is expressed primarily on activated T cells. Crosslinking of the 4-1BB receptor activates an intracellular signal cascade that leads to the activation of NF-kappaB and costimulation of T cell growth. Recent evidence indicates that 4-1BB may preferentially costimulate CD8+ T cell growth and induce cytolytic activity. The cytolytic activity induced by 4-1BB crosslinking is able to eradicate large, well-established, poorly immunogenic tumors and augments allogenic T cell responses in vivo. The 4-1BB/4-1BB ligand costimulatory pathway can provide an alternative T cell costimulatory pathway in the absence of CD28, but may physiologically function as a synergistic or complementary pathway to the CD28 costimulatory pathway. Only some of the basic immunological functions of 4-1BB/4-IBB ligand have been elucidated and much study is required to determine its exact role in T cell activation.