Anti-CD40-mediated cancer immunotherapy: an update of recent and ongoing clinical trials

Abstract

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.

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

“…An alternative approach, blockage of CD40, was well tolerated and able to slightly improve disease severity in Crohn's disease (73). The agonistic CD40 antibodies dacetuzumab and lucatumumab are also safe for patients and are currently being tested for treating malignancies such as chronic lymphatic leukemia, multiple myeloma, and non-Hodgkin's lymphoma (74). Targeting the CD80/86-CD28/ CTLA-4 pathway has also been proven successful in various diseases.…”

Role of CD154 in cancer pathogenesis and immunotherapy

“…Antibodies directed against the CD40 receptor, have been also used alone or in combination in patients with malignancies [99]. In 2007, the first use of an anti-CD40 Ab in patients, termed ''first in man'' study, was reported.…”

Emerging immunological drugs for chronic lymphocytic leukemia

“…CD40 is a transmembrane glycoprotein costimulatory molecule expressed on various antigen-presenting cells (APCs) as well as some tumor cells, including CLL cells [119]. It is a member of the tumor necrosis factor (TNF) receptor superfamily.…”