Immunotherapy treatment for liver cancer in Germany
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Liver cancer is one of the most severe and prognostically unfavorable oncological diseases. In most patients, this tumor cannot be removed due to the advanced stage of the cancer or the low functional reserve of the liver. Radiation therapy and systemic chemotherapy have virtually no effect on liver tumors. However, doctors manage to significantly improve treatment results using immunotherapy. In this publication, we are going to discuss standard and innovative immunotherapy treatments for liver cancer that are used in developed countries.
Content
- When can immunotherapy be used for liver cancer?
- What immunotherapy methods can be used for liver cancer?
- Immune checkpoint inhibitors for liver cancer
- Vaccine therapy
- Adoptive cell therapy
- Where can I undergo immunotherapy for liver cancer?
When can immunotherapy be used for liver cancer?
Hepatocellular carcinoma is an aggressive liver malignancy and the fourth leading cause of death from cancer in the world. More than 800,000 people die from this pathology every year.
The disease can be treated with surgery only at an early stage. But in 80% of cases, HCC liver cancer is detected beyond the stage one-three, when it is no longer possible to remove the tumor. Therefore, the five-year survival rate of patients with primary liver cancer is 15%, and the median survival rate, depending on the stage, is from 6 to 20 months.
Immunotherapy is considered a treatment method that should significantly increase the survival rate of patients with advanced stages of cancer. In addition, it is used after operations and minimally invasive procedures (ablation or chemoembolization) to reduce the risk of cancer recurrence.
What immunotherapy methods can be used for liver cancer?
Immunotherapy has already become the fourth most important treatment method in oncology, after surgery, radiotherapy, and chemotherapy. For some diseases, it demonstrates higher effectiveness compared to cytostatic chemotherapy.
Immunotherapy methods have already been developed that make it possible to achieve long-term remission or cure several types of cancer, even at stage 4. Although the achievements of immune oncology in the treatment of liver cancer are still modest, this direction is considered very promising. Therefore, hundreds of preclinical and clinical studies are now being conducted around the world aimed at assessing the effectiveness of various immunotherapy options for primary liver cancer. More than 30 phase III clinical trials are currently ongoing, so the approval of new drugs and procedures is expected in the near future.
So far, immune checkpoint inhibitors (ICIs) are considered the only standard immunotherapy for liver cancer. A variety of vaccines are also being used in clinical trials, including dendritic cell-based vaccines, oncolytic viruses, and several adoptive cell therapies.
Immune checkpoint inhibitors for liver cancer
The liver is considered an immunotolerant tissue. Everything that is absorbed in the intestines passes through the liver, including a huge number of bacterial and other antigens. Therefore, the immune system is weakened here to avoid unnecessary inflammation and damage.
Liver cells express PD-L1, interleukin-10, prostaglandins, and other immunosuppressive molecules to protect against excessive inflammatory responses. Most patients with liver cancer have increased PD-1 and PD-L1 expression. It is associated with rapid disease progression and poor prognosis because these immunosuppressive molecules interfere with the immune system's ability to inhibit tumor growth.
The mechanism of action of ICIs is based on blocking PD-1 and PD-L1 molecules. As a result of these drugs, the tumor is less able to evade attacks from the immune system.
To date, six drugs from this pharmacological group have already been approved for the treatment of liver cancer. Some are used as first-line therapy for inoperable cancer because immunotherapy for liver cancer is more effective than systemic chemotherapy. Other ICIs are used as second- or third-line drugs. The effectiveness of these drugs is greater when they are combined with the targeted therapy with bevacizumab.
You should not expect that ICIs will be able to cure end-stage liver cancer, but the life expectancy of patients who respond to therapy may increase by several years.
Immune checkpoint inhibitor treatment consists of intravenous infusions at intervals of 2-6 weeks, depending on the drug used. The therapy is well tolerated, especially when compared with chemotherapy. The most common side effect is elevated liver enzymes in the blood. Fever, weakness, nausea, constipation, or diarrhea may also occur.
Vaccine therapy
Many vaccines have already been developed for the treatment of liver cancer, including whole-cell vaccines, peptide-based vaccines, dendritic cell-based vaccines, oncolytic viruses, and DNA agents. Some drugs are already showing significant progress in clinical trials.
Dendritic cell treatment. Great hopes are placed on dendritic cell-based vaccines. Dendritic cells are a type of immune cell that display tumor and other antigens to T cells. With their help, T cells learn to recognize the tumor and attack it more actively.
The essence of the method of treating liver cancer is that blood is taken from a person, dendritic cells are obtained from it, treated with tumor-specific antigens, and injected back into the body. As a result, the antitumor immune response is enhanced.
Currently, most dendritic cell-based vaccines are undergoing phase I and II clinical trials. Several drugs have shown clear success in treating liver cancer. For example, the drug ilixadencel is a dendritic cell stimulated by GM-CSF and IL-4. Early phases of the clinical trials show the vaccine may improve survival in patients, with the effect depending on the dose administered. After injecting 10 million viable dendritic cells into patients with end-stage liver cancer, the median survival rate was 7.4 months, while injecting 20 million cells increased this indicator to almost 12 months.
Oncolytic viruses. These are viruses that destroy cancer cells. They break down, and a large number of antigens enter the bloodstream, which stimulate the immune system. Some drugs show good results, increasing the life expectancy of patients. For example, the oncolytic virus JX-594 (Pexa-Vec) was used at high and low doses in a randomized phase II trial. With the low dose, median survival was 6.7 months, but with the high dose, it increased to 14.1 months.
Adoptive cell therapy
When using this type of liver cancer immunotherapy, doctors collect immune cells from a person's blood, modify them to enhance their antitumor properties, and inject them back into the body. These can be different types of cells, for example, natural killer cells, tumor-infiltrating lymphocytes (TIL), or cytokine-induced killer (CIK) cells.
Great hopes are placed on CAR T-cell therapy because it has proven itself well for some other cancers. So far, early phases of studies are ongoing to evaluate the effectiveness and safety of this treatment method for liver cancer. One study achieved a one-year survival rate of 50.5% and a three-year survival rate of 10.5%, which is not bad considering the advanced stage of the disease. In this study, some patients achieved a partial response (tumor shrinkage by more than a third), and one of them was still alive at the time of publication of the results, although almost 4 years had passed since the CAR T-cell therapy was conducted. It is therefore a promising treatment for liver cancer. Its problem so far is that only a small proportion of patients respond to therapy, but those who respond can count on long-term remission of the oncological disease.
CIK immunotherapy also demonstrates good results. Patients are injected with autologous (their own) cytokine-induced killer cells modified in vitro. A systematic review of 13 phase II and III studies found that CIK cells reduce the risk of relapse and improve survival in patients after liver resection. Patients with tumors larger than 5 cm who received CIK infusions at least 8 times received the greatest benefit from treatment.
Another study of this type of immunotherapy treatment for liver cancer found that CIK was effective in combination with minimally invasive techniques, such as chemoembolization and radiofrequency ablation. The median survival rate of patients who received CIK increased to 56 months compared with 31 months in the control group.
Where can I undergo immunotherapy for liver cancer?
You can travel to Germany to receive immunotherapy for liver cancer at stage 1-3 or at the advanced cancer stages. The best clinics in Germany and around the world already use not only immune checkpoint inhibitors but also cancer vaccines, dendritic cells, oncolytic viruses, CIK, and CAR T-cell therapy.
You are welcome to use the Booking Health service to find out prices, compare the average cost of treatment in different hospitals, and make an appointment. We will help you select the most suitable hospital that uses innovation and demonstrates high success rates in treating liver cancer, and we will organize your trip to Germany.
Choose treatment abroad and you will for sure get the best results!
See the interview for more information:
INNOVATIVE DENDRITIC CELL TREATMENT IN GERMANY – interview with Prof. Dr. med. Frank Gansauge
Authors:
The article was edited by medical experts, board certified doctors Dr. Nadezhda Ivanisova and Dr. Vadim Zhiliuk. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!
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Sources:
Read:
Cancer immunotherapy in Germany
Treatment of stage 4 liver cancer in Germany
Dendritic cell therapy in cancer treatment in Germany - Vaccination against cancer
Adaptive Cell Therapy: CAR T-Cell Therapy
