Targeting CD70 for human therapeutic use.

Expression of CD70, a member of the tumor necrosis factor superfamily, is restricted to activated T-and B-lymphocytes and mature dendritic cells. Binding of CD70 to its receptor, CD27, is important in priming, effector functions, differentiation and memory formation of T-cells as well as plasma and memory B-cell generation. Antibody blockade of CD70-CD27 interaction inhibits the onset of experimental autoimmune encephalomyelits and cardiac allograft rejection in mice. CD70 has been also detected on hematological tumors and on carcinomas. The highly restricted expression pattern of CD70 in normal tissues and its widespread expression in various malignancies as well as its potential role in autoimmune and inflammatory conditions makes it an attractive target for antibody-based therapeutics. This chapter provides an overview of the physiological role of CD70-CD27 interactions and discusses various approaches to target this pathway for therapeutic use in cancers and autoimmunity.