Dendritic cells in the treatment of cancer
General aspects of cancer
Medicine has developed several treatment modalities to fight cancer that can be used by themselves or in combination.
Immunotherapy in cancer
In many cancers, especially if they are advanced, there is a need to develop new treatment strategies as they old ones show little effect. Especially in these cancers there has been an increasing interest in immunotherapies over the last years.
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)
Immunotherapy with dendritic cells
The immune system helps people to stay healthy by recognizing bacteria and viruses as well as cancer cells as noxious and by killing these. It has been know for quite some time that for the recognition of foreign materials (antigens) the body needs antigen presenting cells. These antigen presenting cells alert the immune system to the intruder and activate further immune cells that fight the antigen by various means.
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.
Immunotherapies like all other drugs have side effects. Even though there is only little data, as the therapies are still relatively new and it is difficult to make exact prediction about side effects, our increasing clinical experience and the growing number of clinical trials have given us an initial picture of possible side effects.
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.
There is no data on treatment with dendritic cells during pregnancy; this therefore is an absolute contraindication. If the full blood count shows very low counts of monocytes it may be impossible to isolate them from the blood stream. Other diseases like autoimmune conditions can be contra-indications but need to be discussed on and individual basis during a face to face consultation.
This list may also be incomplete.
Duration of therapy
The treatment usually starts of with a basis immunization of 4 injections spaced 4 to 5 weeks apart. If the tumor shrinks but does not completely regress monthly injections can be continued. If the treatment is successful booster injections every three to six months may be indicated.
Cover of costs
In our experience some German private health care insurers are covering the costs, however many others do not. In some cases patients were successful in courts of law in Germany to get the therapy covered by their private insurers. We do not have experiences with the coverage by non-German insurers unfortunately.
The German state insurance system does not cover the therapy and we do not expect any of the other European state healthcare system to cover the costs unfortunately.