Dendritic cell therapy

Current standard treatment modalities in cancer therapy include surgery, chemotherapy and radiotherapy. Despite signicant advances in standard cancer therapies during the last decades, one challenge of current treatment strategies is the development of daughter tumors (metastases). The spread of tumours, or metastases, is still the most common cause of death from cancer.

Growing evidence indicate that the uninhibited growth of cancer cells results from inappropriate surveillance and control of the immune response. Dendritic cell (DC) therapy based on the concept, that the bodys own defence system (immune system) can effectively recognize and destroy cancer cells. By modication and programming the bodys defence system to attack residual cancer cells expect to be the starting point of cancer metastases. In this way DC therapy is a complementary and supportative approach of current standard cancer therapy . The out-patient clinic MOZAT is a competence centre focussing on the optimisation of aftercare therapy for patients suffering from cancer. Founded by international renowned medical doctors and located in close association to the Rudolnerhaus, an international recognized private hospital located in Vienna, Austria, the out-patient clinic MOZAT have established a DC therapy program to support patients with malignant diseases.

Dendritic cells are key cells for initiation of a cellular immune response
The immune system is the bodys natural defence system against disease. White blood cells, also known as leucocytes, are the effector cells of the immune system. Dendritic cells (DC) are a highly specialized subtype of white blood cells with a unique function. DC can pick up foreign cells or cell particles including cancer cells. Within the DC the cancer cells are destroyed and several pieces of the foreign material are displayed on the cell surface of DC. The exhibition of foreign material on the DC surface is recognized by other cellular effector cells that are then travelling through the body to recognize and destroy tumor cells displaying similar material as expressed by DC. In this way, DC teach the effector cells what type of cells are harmful for the body while the search and the destruction of tumor cells are mediated by specic killer cells. DC therapy based on the nding that DC expressing tumor material of the patients own cancer will introduce a strong immune response against the cancer cells. However, the number of circulating DC in the blood is extremely low which had hindered the clinical application of a DC therapy for a long time. Within the last decade new insights in the biology of DC together with new developments in biotechnology have opened the possibility for generation of DC outside the body. Starting from circulating white blood cells and employing specic culture conditions, it is now possible to generate large quantities of DC within the lab. This opens the possibility for a clinical application of DC immunotherapy as supportative treatment in cancer.

Micrometastases as target for DC therapy

Micrometastases are single tumor cells or small tumor cell clusters shed by solid cancers and disseminated in various organs of the body. Tumor cell dissemination can occur during all stages of the disease, even before the diagnosis of cancer is set. Micrometastases are hard to diagnose, as even the newest diagnostic imaging methods cannot detect tumor cells at the single cell level. Micrometastases have a pronounced clinical impact. Single tumor cells can be the starting point of a recurrence of cancer, which can occur even 5 to 10 years after the primary diagnosis. Micrometastases are the ideal target for a DC therapy. DC therapy can destroy disseminated cancer cells, thereby preventing the development of metastases, slowing the spread of the cancer, and help to extend the life expectancy. Main targets for dendritic cell therapy include disseminated single tumor cells (micrometastases) or metastases of the following epithelial tumors: breast cancer ovarian cancer prostate cancer colon cancer By activation of the bodys own immune system DC therapy is a complementary strategy for the treatment of cancer. According to the current knowledge, however, DC therapy is not a substitute for conventional treatment methods like surgery, chemotherapy, or radiotherapy.

Overview of the DC treatment protocol at the out-patient clinic MOZAT

Enrolment into the DC immunization program starts with a detailed questionnaire about your disease, including an carefully review of your personal records. After a complete medical examination we will discuss the possible advantages of an enrolment in the DC program according to your personal disease history. The treatment protocol consists on three steps: 1) Collection of circulating leucocytes from the blood 2) Generation of DC 3) Injection of DC The treatment protocol starts with the harvest of white blood cells from the circulating blood. Collection is performed using a specic type of machine (cell separator), a worldwide established method for cell harvesting from the circulating blood. A needle is placed in one arm, and your blood ows through a sterile, single use tubing set to the machine. Within the cell separator your blood is centrifuged. White blood cells are collected into a separate sterile bag while other blood cells and the uid parts of the blood return to the body by a second needle placed to the other arm. Medical doctors and specic trained personal closely monitor the whole collection process. After collection the white blood cells are taken to the laboratory where the cells are grown in specic culture medium under strictly controlled conditions. During the culture the cells convert to dendritic cells. At the end of the culture period DC are tested for their maturity, purity and sterility. DC are frozen in liquid nitrogen and are ready for reinfusion. Cell processing and maturation into DC is performed in a specialized lab unit. The whole culture process is performed and monitored by a team of experts with profound experience in the eld of cellular biology and cell culture. The cellular production unit full the national and EU regulatories for the production of cellular therapies. Injection of the DC is performed every 3 to 4 weeks for up to nine months. To guarantee an optimal immune response, the injection is performed under the skin nearby a lymph nodule. At every cell injection DC-induced immune response against cancer cells is monitored by the analysis of your immune status using specic blood tests. Medical doctors with experience in the application of cellular immunotherapies perform the injection of DC. Injection of DC is generally well tolerated and is not associated with adverse side reactions. In some patients DC injection can lead to skin rash, fever, or u-like symptoms. However, the appearance of symptoms are rather a rare and normally disappeared within 2-3 days after the DC injection. In severe cases the symptoms can be controlled by antiphlogistic drugs.

Dendritic cell therapy

mobilization of the immune system to ght against cancer
If you have further questions regarding DC therapy or if you are interested in participating in the DC therapy program of the out-patient clinic MOZAT, please write or call us up. We will assist you.

Dr. med. P. Matthai Univ.Prof. Dr. med. Helmut Renner Univ.Prof. Dr. med. Walter Rhomberg Health and Breast Care Privatordinationen
1050 Wien, Margaretenplatz 2 Austria Fon +43 1 3678008 info@mozat.at www.mozat.at