Novel antibody-based therapeutic agents targeting CD70: a potential approach for treating Waldenström's macroglobulinemia.
Targeting leukocyte differentiation antigens is a validated approach to develop therapeutic agents for the treatment of cancer, autoimmunity, and inflammatory diseases. A subset of activation antigens transiently induced on leukocytes is particularly interesting because many of them are absent from normal tissues, including those of most vital organs, and therapeutic agents' targeting of such antigens is expected to impart limited toxicity. One such antigen, CD70, has recently emerged as an attractive potential drug target for the treatment of cancers. Whereas CD70 is only transiently expressed on activation T and B cells and mature dendritic cells, it is found to be aberrantly expressed on a variety of tumor cells, including Waldenström's macroglobulinemia. In this report, we discuss potential antibody-based therapeutic approaches targeting CD70 for tumor elimination where various mechanisms such as antibody effector functions, immune enhancement, blockade of paracrine growth loop, and delivery of cytotoxic payloads can be exploited to achieve efficacy. Indeed, early clinical trials with therapeutic anti-CD70 antibodies are currently in progress, and those for anti-CD70 drug conjugates will soon follow.
Department of Preclinical Therapeutics, Seattle Genetics, Inc, Bothell, WA 98021, USA.
Che-Leung
CL
Law
Julie A
JA
McEarchern
Iqbal S
IS
Grewal
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D053282:CD27 Ligand / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D053282:CD27 Ligand