Oncology: From research to application in cancer therapy
After an extensive research and development period, immunological treatments for cancer now show results that are superior to the standard therapies (chemotherapy and target therapies). The leading scientific journal “Science” named cancer immunotherapy as the breakthrough of the year in 2013. In 2011 the Nobel Prize for Medicine was awarded to the immunologists Steinman, Beutler and Hoffmann for their research in the area. The principles of the immunotherapy provided at the IOZK are based on their research. In 2010 the first immunological vaccine was approved for prostate cancer.
The doctors and scientists at the IOZK continuously work on translating current research findings in tumour immunology into treatments for their patients while taking into account the regulations of the new European Medicines Act. Our team already practiced along these guidelines before the regulation for new and advanced therapies were put into place. For this reason we are allowed to continue treating patients on an individual patient basis outside of clinical studies.
Through our vaccine the immune system learns to fight the tumour cells
The goal of immunotherapy is to “teach” the patient’s immune system to fight the tumour cells. That is not as simple as it sounds, as the tumour proliferated in the presence of the immune system. The tumour cells need to be presented again to the immune system in a different manner so they can be identified as “dangerous cells”. They are primed with danger signals and are then actively fought by the immune system.
In order to accomplish this, we have developed a vaccine that, amongst other things, contains tumour cells from the patient which have been infected with a virus. Through a series of vaccinations the patient’s immune system is taught to recognise the tumour cells as dangerous and to actively fight these. The virus we use is an avian virus called Newcastle Disease Virus and is not harmful to humans. This virus possesses both anti-tumour and immune stimulating properties and is ideally suited for our purposes.
Elevated temperature places stress on the tumour cells
A further option for altering the tumour cells is the application of different types of hyperthermia (elevating the body temperature). The tumour cells are not killed, but are placed under stress, causing them to produce danger signals and driving them towards programmed cell death (apoptosis). The immune system takes notice of these cell actions and becomes active against the tumour cells.
Dendritic cells play an important role immunotherapy. Without their help, the T-lymphocytes could not recognise the typical markers (tumour antigens) of the tumour cells. Dendritic cells can process tumour cells in such a way that the T-cells can recognise them.
Dendritic cells activate an immune response against the tumour
Dendritic cells are able to activate a specific T-cell immune response against a tumour if they have been loaded with a lysate of stressed tumour cells or NDV-infected tumour cells. The tumour antigen specific T-cells proliferate and develop into killer cells, helper cells and memory cells. The specific killer cells circulate through the entire body and look for tumour cells to destroy these or inhibit their growth.
This principle does not only function in an intact, complete organism (in vivo), but also in cell culture (in vitro). The IOZK makes use of this fact for its patients and produces a patient-specific (autologous) tumour vaccine. It consists of dendritic cells loaded with a lysate of NDV-infected autologous tumour cells. After several vaccinations the T-cell immune response described above is established.
Therapeutic sustainability though memory response
Through the vaccinations an immunological memory is built up against the tumour’s antigens. With these memory cells we achieve a sustained therapeutic effect lasting beyond the end of the treatment. This differentiates us from other therapies. If the memory effect has been activated is tested in our laboratory. If the memory effect has been successfully activated, the immune therapy can be stopped. The memory effect will continue to be monitored at regular intervals and can be reactivated should it show any signs of receding.
Why is the memory effect of such importance? As with any other type of tissue, there are stem cells within the tumour tissue. They retain the structural information of the respective tissue. This is also the case for tumour stem cells and tumour tissue. Tumour stem cells can leave the tumour during the early stages of tumour growth and settle in other tissue structures. There the tumour stem cells initiate new tumour growth know as metastases. Sometimes the tumour stem cells to not initiate tumour growth immediately, but remain dormant for a while and are activated at a later stage.
These tumour stem cells are not targeted by the standard therapies currently available, such as chemo-, target- or anti-body therapies. Due to this, tumour growth can always reoccur after these therapies. Hence a sustainable, tumour-specific, cytotoxic immune response, the memory effect, is so important. If a dormant tumour stem cell becomes active, the immunological memory is activated and new tumour growth is prevented.
A view on new target therapies
What differentiates our autologous vaccine from modern target therapies or tumour vaccines using standardised antigens? Target therapy vaccines are aimed at blocking a certain target structure on the tumour cell. If such a target structure is identified (through special diagnostic histology), then the application of the target therapy or the standardised vaccine is possible.
Unfortunately, in most cases, the therapeutic effect is not sustained. Why is this the case? It has recently become apparent that solid tumours can consist of many different mutations within the same tumour tissue. If only one of these structures is blocked, then, after a short period of restructuring, the remaining structures of the tumour previously not blocked, can lead to further growth. For this reason we use the patient’s own tumour tissue which contains the whole spectrum of structures. This provides the most promising option for establishing a broad and effective immunological anti-tumour response.
Individual strategies when selecting a therapy against cancer
In addition to immunotherapy, the IOZK uses further treatments to enhance the therapeutic effect, all while adhering to the regulations pertaining to the production of autologous tumour vaccines as outlined by the Medicines Act. The therapy is based on dendritic cells loaded with autologous tumour lysate that is obtained though NDV infection. In addition, the treatment may be combined with hyperthermia to further enhance the effect.
On an individual patient basis it needs to be assessed if our treatment can be used as an auxiliary to standard therapy or in conjunction with other advanced therapies. It has been shown that a single treatment approach is not optimal when dealing with such complex diseases as malignant tumour growth.
We want to emphasise that all future treatment options remain open to the patient after the removal of the tumour and processing of the tumour material at the IOZK. In order for this to be possible, it is imperative that the patient takes up contact with the IOZK prior to tumour removal, so that the optimal treatment can be guaranteed.