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.