Cancer is one of the biggest challenges for modern medicine. According to Robert Koch Institute in Germany in 2010 there were about 450,000 new cases. Though there are different therapies in general most of the malign tumors are not curable. Further, cancer is highly heterogeneous. Two persons who suffer from the same type of cancer, can show totally different variations and ways of progress. That makes it hard to treat the cancer and just for that reason oncology is one field where personalized medicine is advancing extremely fast. The more that treatments can be tailored to the single patient, the higher are the chances for treating that patient’s cancer effectively. Personalization – creating a special tailored therapy for everybody -- wasn’t possible before. The goal is to allow patients a pain free time at least for a while, and to dam up the growth of the tumor.

To reach that goal, these times especially some biotechnology companies concentrate on the power of the human immune system. To strengthen this natural defense of the body, the companies are using immune cells obtained from the patient’s blood and (outside the body, in a lab facility) exposing these immune cells to biomarker fragments of the cancer cells, to “educate” the immune cells to recognize the tumor and attack it, similar to the way that immune cells are “educated” to recognize regular germs after an immunization.

The Fraunhofer Institute for Cell Therapy and Immunology (IZI) supports different international companies at the production of new immune cell based treatments. IZI is taking care of the approval of the manufacturing methods in Europe and the preparation of the immune cell treatment for testing in clinical trials. “Right now we are transferring the process from America to our institute and adjusting it to the European market”, explains Dr. Gerno Schmiedeknecht, leader of the department for cell technics at the IZI. “The development of a new medicament requires much time and effort; that’s why the experience and the equipment of the Fraunhofer-Institute are so helpful for the foreign partners. After adapting the products for Europe, the IZI will produce these novel immune cell treatments for the clinical trials in Europe.”

A partner of the Fraunhofer IZI, the American company Northwest Biotherapeutics Inc. has been researching for more than a decade on a body-own immune therapy against the most aggressive form of brain cancer: GBM (“Glioblastoma multiforme” brain cancer). In the US, the remedy DCVax® Brain is already under way being tested in a phase 2 clinical trial which will include 240 patients. With the help of the Fraunhofer IZI, the medicine shall soon be made accessible for the European patients. Dr. Gerno Schmiedeknecht is hopeful that this complex and individual therapy could become a success. But he also knows that a lot of work and research is to be done for a further development of personalized products. “Behind this therapy hides a very elaborate process. We need parts of the tumor and healthy immune cells, than we have to clean and to cultivate them before we can combine them in the laboratory. All these steps are not yet automatized and constitute much complex handwork.”

Tumor cells as an immunization

The general approach of this immune therapy is to take some of the patients own white blood cells, called Monocytes, which are the precursors of Dendritic cells, and convert them into a fresh new batch of Dendritic cells in a lab facility, outside the body, where they are not compromised by the body-wide effects of cancer. Then, the fresh new batch of Dendritic cells are combined with fragments of the cut out tumor. The Dendritic cells absorb those tumor fragments and present parts of them on their surface, like signs. The “educated” Dendritic cells carrying these signs on their surface are then injected back into the patient’s body, and the signs on the surface of Dendritic cells then serve to notify other parts of the patient’s immune system (including the T cells, the B cells that make antibodies, and many others) that any tumors having the same biomarkers as are displayed on the Dendritic cells should be attacked. 

In this way, the immune system is taught which (malignant) cells it has to fight, similar to the process by which immunization against the flu teaches the immune system to recognize and attack the flu virus.   When the “educated” Denditic cells are injected back into the patient’s body, they become a kind of commander of the whole human immune defense apparatus and they mobilize all different parts of the immune system against exactly those cancer cells whose biomarkers are displayed like signs on the surface of the Dendritic cells.

Immune therapies like these have a significant advantage compared with conventional drugs:  the immune cells are “smart” and can actively distinguish between healthy and malignant cells. Another advantage of immune therapies is that they work by mobilizing natural processes, and do not involve any toxic compounds like chemotherapies do.  As a result, immune therapies are followed by virtually no unwanted side effects, and are much more agreeable and safer than chemotherapy.  Patients taking such immune therapies do not become ill, or have their hair fall out, or have to stop working;  instead, the patients go right on with their normal lives.  But immune therapies are not a replacement for a surgery – on the contrary, surgery and immune therapies are complementary. “DCVax® is just an additional form of therapy, an immunization next to the standard treatment”, emphasizes Gerno Schmiedeknecht. “Nearly all patients with the present standard therapy (surgery plus radiation and chemotherapy) are facing a rapid recurrence of the tumor, and that’s what we want to prevent or at least to delay to offer our patients a longer survival with good quality of life.”

Until this kind of immune therapy is sold on the market, it will take some more time.  The therapy is now in late stage development after more than a decade of work up till now. A large, 240-patient clinical trial is well under way in the US, and is planned to include 90 patients in Germany next spring. The results from two prior Phase I/II clinical trials in the US are promising:  the median time until patients have recurrence of their tumor is only 6.9 months with standard of care (surgery plus radiation and chemotherapy) but was 2 years in patients treated with DCVax®;  median survival time is only 14.6 months with standard of care but was 3 years in patients treated with DCVax®.  Moreover, none of the patients treated with DCVax® experienced any toxic side effects. If the results in the large clinical trial now under way in the US (and planned to include Germany next spring) are similar to these prior trial results, the American company Northwest Biotherapeutics plans to seek accelerated approval in order to make the treatment widely available to patients as soon as possible.