Dendritic cells in the treatment of cancer

The immune system consists of numerous substances and cell that are used as tools in different research and study protocols.

Although we are far from understanding all the interactions within the immune system and within the human body, several medicals have been developed and licenced that use immunologic principles:

• First antibody to be used in cancer treatment: Trastuzumab / Herceptin® in metastatic breast cancer overexpressing the receptor Her2/neu (USA, 1998)
• First vaccination to prevent cervical cancer: Gardasil® (USA, 6/2006) und Cervarix® (Australia, 5/2007);
  (Nobel Prize in medicine 2008 for Harald zur Hausen for the discovery that cervical cancer largely is caused by human papillomavirus infections)
• First autologous cell based immunotherapy with dendritic cells: Sipuleucel-T / Provenge® in hormone resistant prostate carcinoma (USA, 4/2010)
  (Nobel Prize in medicine 2011 for Ralph M. Steinman for the discovery of dendritic cells and their role in the adaptive immune)
  

Amongst the most important antigen presenting cells are the dendritic cells. They have tree like arms (Greek: Dendron=tree) with which they search the lymphatic fluids for foreign materials.

Cancer cells differ from healthy cells. This difference is harnessed by immunotherapy by fighting the cancer with the bodies own immune system.

Antigen presenting cells in the skin, the Langerhans cells, have been shown to be highly relevant during the process of preventative vaccinations. There are also a few of these dendritic cells in the blood stream. These were first described by Steinman and Cohn in 1973 (Nobel Prize in medicine 2011 for R. M. Steinman).

In addition to being able to isolate small amounts of dendritic cells from the blood or the bone marrow, they can be grown from precursor cells in the bloods, so called monocytes. Only the discovery that they originate from the myeloid lineage made it possible to produce larger quantities of antigen presenting cells easily (Peters et al., 1987).

During immunotherapy with dendritic cells a subgroup of white blood cells of a patient, the monocytes, harvested through conventional blood taking or leukapheresis, is isolated. In the laboratory these monocytes are differentiated into antigen presenting cells, the monocytic dendritic cells, by addition of cellular messengers (cytokines, growth factors).

During this time the immature dendritic cells can additionally be “made aware” of the cancer by for instance adding lysed tumor cells or known tumor antigen peptides to the cells. The immature dendritic cells can take up tumor antigen or lysed tumor cells and present important parts of these on their surface. This process is called priming. In addition dendritic cells are capable of taking up tumor antigens in the patient’s body and this can be enhanced by giving certain cellular messengers.

Depending on the individual situation of the patient and the properties of the tumor each patient will receive an individual stimulation protocol.

After 7 days the primed and activated dendritic cells are injected into the skin or a vein of a patient. Sometimes there will be concurrent immunological stimulation with cellular messengers locally as this can improve the immune response in certain cases.

Flu-like symptoms like fever, rigors, tiredness as well as swelling and itching at the injection side are common side effects. These usually go away by themselves quickly and rarely need treatment or can be treated with fever lowering drugs, anti-allergy and anti-pain medications without problems.

Additional side effects can depend on the type and position of the tumor. Other side effects we or other groups observed include: Nausea, diarrhea, vomiting, reactivation of an autoimmune disease, rheumatoid arthritis, low platelets, anemia as well as undesirable side effects like those that can be encountered after any injection or infusion.

Altogether our experience shows that the common side effects occur in the days immediately after the injection.

This list of possible side effects on this website does not claim to be complete and there may be possible unknown side effects.

During the face to face consultation you should discuss the type and duration of possible general and individual side effects in relation to the desired therapeutic effects.