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Cervical cancer treatment with dendritic cell therapy | Booking Health

Cervical cancer treatment with dendritic cell therapy

The article was reviewed by an expert in the field of medicine Prof. Dr. med. Frank Gansauge
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Dendritic cells are used in progressive medical centers to create personalized cancer vaccines. The drug is made for a specific patient from their own blood and then used to enhance the antitumor immune response. This experimental treatment is already showing good results in clinical trials. You are welcome to use the international Booking Health service if you want to undergo this procedure, find out the cost of cancer treatment, and make an appointment with a doctor in one of the German hospitals.

Content

  1. What are dendritic cells?
  2. The role of immunotherapy in cervical cancer treatment
  3. Research findings
  4. Dendritic cell activation by the MTBHsp70-exFPR1 protein
  5. Dendritic cell therapy for early-stage cancer
  6. Dendritic cell therapy for end-stage cancer
  7. What is the process of cancer treatment?
  8. What results can be expected?
  9. Where to undergo dendritic cell therapy for cervical cancer?

What are dendritic cells?

 

Immunotherapy for cancer is considered one of the most promising areas of medicine. It is with this that the upcoming breakthrough in cancer treatment is associated. Some immunotherapy methods have already proven themselves to be effective, allowing for the suppression of the development of cancer for a long time or even curing cancer in advanced stages.

Dendritic cells (DC cells) are one of the tools used to stimulate an antitumor immune response. They are immune cells that "learn" the antigen themselves and then "train" the T cells to fight the foreign agent in the body.

More than 300 studies are currently being conducted around the world using dendritic cells for various malignant neoplasms. Doctors are also trying to use this method for cervical cancer. Perhaps it will be possible to reduce the risk of relapse after surgery or control cancer at an advanced stage for longer with their help.

Dendritic cells are considered the most powerful specialized antigen-presenting cells. They have the unique ability to activate unsensitized T cells, thereby triggering a cellular antitumor response. Immature dendritic cells (imDCs) take up and process antigens. Mature dendritic cells (mDCs) then stimulate T cells that attack the tumor. They play a key role in transmitting information about antigens from peripheral tissues to areas of lymphoid tissue.

The role of immunotherapy in cervical cancer treatment

 

Cervical cancer is the most common gynecologic cancer in the world. Interestingly, this is one of the few oncological diseases against which one can be vaccinated. Almost all cases of cancer of the cervix are associated with the human papillomavirus. Vaccines have been developed against it to protect against infection. But in most countries in the world, total vaccination of the population is not carried out, and screening programs are poorly organized, so the incidence of cervical cancer remains very high. Almost half a million new cases are reported worldwide every year.

The standard treatment methods for the disease are surgery and radiation therapy. Cytostatic chemotherapy is also widely used. New directions of drug treatment, such as targeted therapy and immunotherapy, are still not widely used for malignant tumors in the cervix.

In standard treatment regimens, immunotherapy can only be used in a limited number of patients if the tumor has increased PD-L1 protein expression. Only one PD-1 inhibitor is approved for clinical use, and it is applied as second-line therapy or for the suppression of recurrent tumors.

The progress of effective immunotherapy strategies is, however, ongoing. There are more and more cervical cancer vaccines that are undergoing clinical and preclinical studies. They are inactivated viruses, live attenuated (weakened) bacteria, peptides and proteins, nucleic acids, and cellular vaccines that use dendritic cells loaded with antigen. E6 or E7 is most often used as an antigen. These are proteins from the virus that causes cancer. 

Research findings

 

So far, we do not have any statistics on how dendritic cells work in cancer of the cervix because treatment is not standardized and experience is limited to a few studies.

Typically, researchers assess the severity of the immune response in laboratory animals or humans, assess safety, and select doses. Some studies evaluate the results of clinical use. The vaccines used by different authors, the methods of their production, and their application differ significantly.

 

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Dendritic cell activation by the MTBHsp70-exFPR1 protein

 

For dendritic cells to work, they need to "‎learn" an antigen, which is present in large quantities in cancer cells. In this case, T cells will attack it, while healthy tissues will not be affected by the autoimmune process.

Scientists used the FPR1 protein as an immunotherapeutic target in preclinical studies. It is found predominantly in cancer cells and is present in very small quantities in normal tissues. It is a protein that is involved in inflammation, wound healing, and antimicrobial defense.

Dendritic cells were treated with the MTBHsp70-exFPR1 protein to activate them. It is obtained from the bacterium that causes tuberculosis. Under the influence of this protein, the expression of CD80 and CD83 in dendritic cells increases. The production of cytokines, substances that enhance the immune response, also increases. Under the influence of MTBHsp70-exFPR1, the production of TGF-β1, IFN-γ, and IL-12 dendritic cells increases.

The drug was tested in experiments on mice. They were injected with activated dendritic cells, and, as a result, tumor growth was suppressed. The effect is associated with the inhibition of cell proliferation (division) as well as increased apoptosis (programmed cell death). Proliferation was reduced due to the release of cytokines. Apoptosis is caused by T cell cytotoxicity.

The authors of the study concluded that dendritic cells activated by the MTBHsp70-exFPR1 protein could be used to treat cervical cancer in women. So far, no clinical studies have been conducted on this treatment option.

 

Cervical cancer treatment with dendritic cell therapy

 

Dendritic cell therapy for early-stage cancer

 

Another version of the dendritic cell vaccine against cancer of the cervix has reached clinical trials. In the first phase, scientists tested the drug at cancer stages IB and IIA.

These stages are considered curable. You can undergo surgery or radiation therapy to get rid of cancer, but there is no 100% guarantee of a cure. Even if no cancer cells are found in the removed lymph nodes, the disease will recur within 5 years with a 20% chance. If metastases are detected in distant lymph nodes, the risk of relapse is even higher and reaches 50%.

J Virol et al. suggested that the use of dendritic cells may reduce the risk of relapse. But since this was the first phase of the study, the main task was not so much to assess the effectiveness of the dendritic cell vaccine as to select optimal dosages and assess the toxicity of treatment and the severity of immune reactions.

Treatment is based on the presence of a connection between cervical cancer and human papillomavirus infection. Most cases of the disease are caused by HPV types 16 and 18. They produce oncoproteins E6 and E7, which cause transformation of the epithelium of the cervix. These proteins are found in almost 100% of tissue samples obtained during a biopsy. Scientists therefore suggested that these viral proteins could be used by the immune system as targets for attacks.

Preliminary clinical studies have found that the dendritic cell vaccine can rapidly generate broad T cell immunity in healthy individuals and is capable of inducing regression of tumor metastases without any significant side effects in patients with malignant neoplasms, including lymphomas and melanomas. These successes encouraged the authors of the study to develop technology for cervical cancer therapy.

If dendritic cells are grown for 5-7 days with granulocyte macrophage colony-stimulating factor and interleukin-4, the dendritic cells are good at capturing antigens and producing many cytokines. However, they remain sensitive to the immune-weakening effect of interleukin-10 secreted by the tumor. It is used to suppress the antitumor response. If dendritic cells are fully matured, their phagocytic activity (the ability to absorb and "digest" foreign particles) decreases, but the production of cytokines, such as interleukin-12, increases.

The scientists used increasing doses of mature autologous (the patient's own) dendritic cells treated with the full-length HPV16/18 E7 oncoprotein and hemocyanin. Their task was not to assess survival rates. The researchers only tested the toxicity and severity of the immune response. However, during the observation period, no recurrence of cervical cancer was recorded.

A total of 10 patients participated in this study by the University of Arkansas. Three were given a low dose of the cancer vaccine, another three were given a medium dose, and four were given a high dose. Patients had not received steroids, chemotherapy, or radiation therapy for at least 4 weeks before starting dendritic cell treatment. Previously, all women had undergone radical surgery: a hysterectomy (removal of the uterus) or a trachelectomy (removal of the cervix). One patient also underwent radiation therapy due to risk factors for disease recurrence. All women had "clean" lymph nodes without any signs of metastases based on the results of the pathomorphological examination.

The specialists collected blood from people, performed leukapheresis, and obtained immune cells. Some were preserved, and some were immediately used to obtain dendritic cells. Prior to the injection, the number of cells and their viability were assessed, and the vaccine was checked for safety. A minimum of seven doses for each patient were frozen. The cervical cancer vaccine was injected five times at 3-week intervals. The injections were made subcutaneously in the thigh.

Patients were followed up according to a standard regimen, taking into account the stage of cancer. Pelvic examinations and Pap smear tests were performed every 3 months for the first 2 years and every 6 months thereafter. Computed tomography of the abdomen and pelvis was performed annually or as clinically indicated.

During the follow-up period, no cases of toxicity were recorded. The patients had no complaints, although the researchers found redness in the injection area, and in some women, the inguinal lymph nodes were enlarged. This is more good than bad, since such reactions indicate that immunity has worked.

The main goal of the study was to assess the immune response to the injection of dendritic cells, so all patients were tested for antibodies to E7 and HPV16/18, cytokines, and immune cells. The results were assessed after the third and fifth doses, as well as 2 months after the completion of the vaccination course. Scientists have recorded the cellular and humoral immune responses, so they came to the conclusion that the dendritic cell vaccine can be used for the following:

  • Destruction of tumors with a low tumor burden
  • Prevention of relapses in immunocompetent patients

Dendritic cell therapy for end-stage cancer

 

In cases of metastatic cervical cancer, dendritic cell therapy is complicated by the fact that the patient is in a state of suppressed immunity. The patient is weakened due to chemotherapy.

But still, at this stage, some studies have demonstrated encouraging results. The most impressive came from a placebo-controlled trial, Ramanathan, Priya et al. In one patient with metastatic cervical cancer and a high tumor burden, all tumors disappeared after the completion of therapy with dendritic cells treated with tumor lysate and cisplatin. The cancer did not recur within 6 years of follow-up.

What is the process of cancer treatment?

 

Treatment differs from hospital to hospital. It is not standardized because dendritic cell immunotherapy for treatment of cervical cancer is still an experimental therapeutic method.

A general treatment regimen looks as follows:

  1. Dendritic cell harvesting. They can be harvested from a variety of tissues, but usually blood is the main source. It contains monocytes, and dendritic cells can be harvested from monocytes.
  2. Dendritic cell processing. What is needed is a reaction with the antigen so that the dendritic cells take up these molecules and then transmit the antigen data to the T cells in the human body. Additional manipulations may sometimes be performed to increase cell survival rates. The longer they live, the more T cells will learn to recognize and attack the tumor. Therefore, additional RNA fragments can be added to them, which block apoptosis (self-destruction).
  3. Dendritic cell injection. It is still unknown how, where, how often, and how many times dendritic cells should be injected to obtain optimal therapeutic results for cervical cancer. Scientists are trying to find out through research. For example, Gene Therapy published the results of experiments on mice that were conducted to determine the optimal method of injecting dendritic cells for cervical cancer. The researchers used the following three routes of injection: subcutaneous, intravenous, and intramuscular. It turned out that intramuscular injections allow for the most pronounced immune response to be achieved. The mice had the highest levels of T cell precursors, CD8, CD4, and specific antibodies.

 

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What results can be expected?

 

The main question that patients want to know the answer to is what result they will get from dendritic cells for cervical cancer. Unfortunately, there is still no complete answer to this question. We do not know how effective dendritic cells for cervical cancer are. We know from research that some women have excellent results, especially when immunotherapy is combined with other treatment methods.

Response to treatment at different stages of cervical cancer

Stage of cancerStandard treatmentsAlternative medicine methodsDendritic cell vaccination
Localized cancerAbout 100%Not usedNot used
Locally advanced cancerUp to 60-80%Not usedNot used
Metastatic cancerUp to 20-40%Up to 50%Up to 70%

The development of dendritic cell-based vaccines is ongoing, and the drugs are being improved, although many problems have not yet been solved, such as:

  • Creating a personalized vaccine for each patient is expensive
  • Different hospitals use different cultivation methods, which makes it difficult to standardize the treatment method
  • The optimal methods of dendritic cell injection, timing, and doses have not yet been determined

Scientists are working to eliminate these shortcomings. While research is ongoing, some hospitals have already begun using dendritic cell-based vaccines for cervical cancer treatment. This therapeutic option is usually offered to those who do not respond to standard medications and procedures.

One of the main benefits of the treatment is that dendritic cell vaccines are safe. In addition, they are compatible with any other drugs and treatments, as well as other vaccines. They can be used either as monotherapy or in combination with other immunotherapies, such as immune checkpoint inhibitors.

DENDRITIC CELL THERAPY - Professor Frank Gansauge

Where to undergo dendritic cell therapy for cervical cancer?

 

Immunotherapy and cell therapy for cervical cancer are available in Germany.

Dendritic cell vaccine therapy is not yet used as a standard procedure. However, some hospitals in Germany are already giving their patients the opportunity to use this advanced technique.

You are welcome to use the Booking Health service if you want to undergo your cancer treatment in Germany. On our website, you can find out current prices, find out information about leading hospitals in Germany and their doctors, choose the most suitable medical center, and make an appointment for your treatment in Germany for your preferred dates. Our company's employees will help you select the most suitable hospital, reduce the waiting time for cancer treatment, and also take care of organizing your trip.

On the Booking Health website, you can find out the cost of procedures in different medical centers in Germany and compare prices. Cancer treatment will cost you less if you use our service. The cost of services will be lower due to the absence of taxes for foreigners.

The initial price of the program is final, which means that it will not increase even if additional medical procedures are required. Price stability is ensured due to the fact that you will receive insurance against unexpected expenses. The cost of all unnecessary procedures will be covered by the insurance company.

The Booking Health specialists will take care of arranging your trip to Germany for cancer treatment. We will help you prepare the necessary documents, book a hotel room, purchase airline tickets, meet you at the German airport, and take you to the hospital by car. After the completion of your treatment in Germany, a return transfer will be arranged for you.

 

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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!

Our editorial policy, which details our commitment to accuracy and transparency, is available here. Click this link to review our policies.

 

Sources:

National Library of Medicine

Science Direct

Cancer Cell International

 

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