Targeting CD40 in Waldenström's macroglobulinemia.
CD40 is a member of the tumor necrosis factor (TNF) receptor family and is expressed in a majority of B-cell malignancies. In Waldenström's macroglobulinemia (WM), CD40 expression is a common feature of bone marrow infiltrating lymphoplasmacytic cells, and preclinical evidence suggests that CD40 signaling is functionally important for WM growth and survival. Two antibodies targeting CD40 (SGN-40 and HCD 122 [Chir 12.12]) are currently undergoing clinical testing in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). HCD122 is a novel, fully human, IgG1 antagonistic monoclonal antibody while SGN-40 is a humanized IgG1 partial agonistic antibody. Both agents have demonstrated activity in preclinical models and are potent mediators of antibodydependent cellular cytotoxicity (ADCC). Clinically, phase I data suggest both agents are well tolerated with no immunogenicity and have early evidence of single-agent clinical activity in relapsed and refractory NHL and MM. These observations support the testing of CD40-targeted agents in WM.
Oncology Division, Stanford University Medical Center, Stanford, CA 94305, USA.
Mark
M
Lee
Ranjana
R
Advani
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens