The costimulatory molecule CD40 is a member of the tumor necrosis factor (TNF) 
receptor superfamily and is expressed on various antigen presenting cells (APCs) 
as well as some tumor cells. The binding to the natural ligand CD40L, which is 
expressed on T helper cells, leads to APC activation and thus enhancement of 
immune responses. Treatment with anti-CD40 monoclonal antibodies has been 
exploited in several cancer immunotherapy studies in mice and led to the 
development of anti-CD40 antibodies for clinical use. Here, Dacetuzumab and 
Lucatumumab are in the most advanced stage and are being tested as treatment for 
malignancies such as chronic lymphatic leukemia (CLL), Multiple Myeloma (MM), 
and non-Hodgkin's lymphoma (NHL). The promising results from these early 
clinical trials have encouraged clinical drug development in order to 
investigate the effect of CD40 mAbs in combination with other cancer 
immunotherapies, in particular interleukin (IL)-2. An in-depth analysis of this 
immunotherapy is provided elsewhere. In the present review, we provide an update 
of the most recent clinical trials with anti-CD40 antibodies. We present and 
discuss recent and ongoing clinical trials in this field, including clinical 
studies which combine anti-CD40 treatment with other cancer-treatments, such as 
Rituximab and Tremelimumab.