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

TY - JOUR

T1 - Anti-CD40-mediated cancer immunotherapy

T2 - an update of recent and ongoing clinical trials

AU - Hassan, Sufia Butt

AU - Sørensen, Jesper Freddie

AU - Olsen, Barbara Nicola

AU - Pedersen, Anders Elm

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

U2 - 10.3109/08923973.2014.890626

DO - 10.3109/08923973.2014.890626

M3 - Journal article

C2 - 24555495

SN - 0892-3973

VL - 36

SP - 96

EP - 104

JO - Immunopharmacology and Immunotoxicology

JF - Immunopharmacology and Immunotoxicology

IS - 2

ER -