Treatment of Cancer with Dendritic Cells

General Information on Cancer Treatments

Medicine has developed various treatment options to combat cancer, which can be used individually or in combination.

Immunotherapies for Cancer

For many cancers, especially in advanced stages, the limited effectiveness of standard therapies has made it increasingly necessary to develop new treatment approaches. In recent years, there has been growing interest in immunotherapies.
The immune system is made up of a variety of substances and cells, which serve as tools in different research and study approaches.
Although not all interactions within the immune system and the human body are fully understood, medications using immunological principles have already received approval:

• First approval of an antibody therapy for cancer: Trastuzumab / Herceptin® for metastatic breast cancer with Her2/neu overexpression (USA, 1998)
• First approval of a vaccine for the prevention of cervical cancer with HPV vaccines Gardasil® (USA, 6/2006) and Cervarix® (Australia, 5/2007)
  (2008 Nobel Prize in Medicine to Harald zur Hausen for discovering the link between human papillomaviruses and cervical cancer)
• First approval of an autologous cellular immunotherapy with dendritic cells for hormone-refractory prostate cancer: Sipuleucel-T / Provenge® (USA, 4/2010)
  (2011 Nobel Prize in Medicine to Ralph M. Steinman for discovering dendritic cells and their role in adaptive immunity)

Immunotherapy with Dendritic Cells

The immune system keeps humans healthy by recognizing and destroying harmful agents such as bacteria, viruses, and cancer cells. It is now known that so-called antigen-presenting cells are required to detect foreign bodies (antigens). These cells alert the immune system to intruders and activate other immune cells to fight them using different mechanisms.
Among the most important antigen-presenting cells are dendritic cells. They have tree-like extensions (Greek dendron = tree), with which they search for foreign bodies as they travel through lymph and blood.
Cancer cells differ from healthy cells. Immunotherapy takes advantage of this “foreignness” to stimulate the body’s defenses against cancer.
Antigen-presenting cells in the skin, called Langerhans cells, have proven useful in traditional preventive vaccinations. In the blood, antigen-presenting cells appear in small amounts as dendritic cells, first described by Steinman and Cohn in 1973 (Nobel Prize 2011 for R. M. Steinman).
In addition to isolating dendritic cells directly from blood or bone marrow, they can also be generated from precursor cells in the blood called monocytes. Clarifying their origin in the myeloid lineage made it possible to produce larger quantities of antigen-presenting cells more easily (Peters et al. 1987).

For dendritic cell immunotherapy, a patient’s monocytes—a subgroup of white blood cells—are collected through a standard blood draw or leukapheresis. In a cleanroom laboratory, these monocytes are differentiated into antigen-presenting cells (monocyte-derived dendritic cells) using cellular signaling molecules (cytokines, growth factors).
During this process, the still “immature” dendritic cells can also be exposed to cancer-related material. They can absorb and process tumor antigens or tumor lysates, and later present important tumor markers on their surface to the immune system. This process is called priming. Dendritic cells are also capable of capturing tumor antigens directly inside the patient’s body and can be activated by cellular messengers.
Depending on the patient’s condition and tumor characteristics, stimulation protocols are individually tailored.
After seven days in culture, the “trained” and activated dendritic cells are administered back to the patient, either into the skin or intravenously, similar to a vaccination. Sometimes additional immune stimulation with local cytokine application is performed to further boost the immune response.

Side Effects

Like all medications, immunotherapies also have side effects.
Since these therapies are relatively new, the data available is not as comprehensive as for long-established treatments. However, with growing clinical experience and more published studies, certain assessments can be made.
Common side effects include flu-like symptoms such as fever, chills, fatigue, and redness, swelling, or itching at the injection site. These usually resolve on their own or can be easily managed with fever-reducing, antiallergic, or pain-relieving medications.
Other side effects may depend on the tumor’s location and type.
Rarely reported side effects, either observed by the treating teams or published by other groups, include nausea, diarrhea, vomiting, reactivation of autoimmune diseases, rheumatoid arthritis, thrombocytopenia, anemia, and general risks associated with injections and infusions.
Overall, most side effects appear in the days immediately following treatment.
This list of side effects is not exhaustive, and new, previously unknown reactions cannot be ruled out.
The doctor and patient should discuss the potential type and duration of general and individual side effects in relation to the expected therapeutic benefit.

Contraindications

Since there is no experience with dendritic cell treatments during pregnancy, an existing pregnancy is an exclusion criterion. Very low blood cell counts may make monocyte collection impossible. Other conditions, such as autoimmune diseases, may also be exclusion criteria and require individual risk assessment between doctor and patient.
This list is not exhaustive.

Duration of Treatment

Treatment is usually carried out as a basic immunization four times, each 4–5 weeks apart. If the tumor does not fully regress but responds, monthly vaccinations may be recommended until complete remission. If successful, booster vaccinations at longer intervals of three to six months may also be useful.

Coverage of Costs

In our experience, some private health insurance companies cover the treatment costs, though many deny coverage. In some cases, courts have ruled that private insurers must pay.
Statutory health insurance generally does not cover the costs, even though the German Social Code V requires coverage under certain conditions (Social Code V amendment of 01.01.2012, §2 paragraph 1a).