Immunotherapy for metastatic melanoma according to the TIL protocol (tumor-infiltrating lymphocytes)
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Melanoma is one of the most aggressive malignant formations. It takes the lives of young people: many patients are in the age category of 30-40 years. Melanoma develops rapidly and metastasizes early. At the same time however, this tumor is one of the most susceptible to immunotherapy. This type of treatment achieves good results even in metastatic tumors. The doctors abroad use immunotherapy according to the TIL protocol (i.e. tumor-infiltrating lymphocytes) for the treatment of melanoma at its advanced stages.
Content
- Briefly: what is TIL?
- Is this a new treatment method?
- Why does it work?
- How is the treatment carried out?
- Is it always possible to obtain cells for the treatment of melanoma?
- The results
- Enhanced protocols
- Is the treatment safe?
- How can I get TIL therapy?
Briefly: what is TIL?
TIL therapy is based on the separation and cultivation of tumor-specific lymphocytes. These are white blood cells which are responsible for immunity.
During the treatment, the patient’s own lymphocytes are obtained from the tumor tissue. They are located inside the melanoma, as they migrate to the tumor to fight cancer.
The next step is the activation of these cells and their cultivation in laboratory conditions. Then, the cells are injected back into the patient's body.
This method is combined with chemotherapy. The use of chemotherapy avoids the suppressive effect of immunity on the injected white blood cells. The drugs which do not suppress bone marrow are used.
Nowadays, TIL is used in the treatment of several types of cancer. The greatest success was achieved in the treatment of melanoma. In some patients, it is possible to achieve complete regression of the neoplasm and all metastases, even in metastatic tumors.
Is this a new treatment method?
TIL is not a new treatment method. Therefore, TIL refers to well-studied techniques. Oncologists have studied not only the immediate, but also the long-term results of this immunotherapeutic technique.
The first TIL trials on mice were carried out in 1986. In 1988, clinical trials on humans began. In 1992, the results from research illustrating the use of TIL in combination with a high dose of interleukin-2 were published. About 34% of patients responded to the treatment, 6% of these patients showed a complete response.
Since then, the technique has been improved, and today's results are much better than those that were reached 30 ago.
Why does it work?
Our immunity can destroy cancer cells and does so all the time. It has long been known that people with an acute immunity suppression (for example, HIV patients) suffer not only from infections, but also from malignant tumors.
Melanoma can defend itself against immunity. Therefore, despite the migration of lymphocytes into the tumor, they cannot destroy it. There are several reasons for this:
- insufficient number of cells;
- their low tumor reactivity;
- excretion of substances by tumor, which reduces the activity of the immune cells.
These problems are solved during the treatment, according to the TIL protocol. The immune cells are extracted from the tumor and cultivated in a laboratory in order to increase their number. At the same time, their reactivity increases. The cells develop without inhibiting tumor action, so, when they are injected into the body, the doctors usually obtain a good response to treatment. In the most favorable cases, the tumor and its metastatic foci are completely destroyed by the immune cells.
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How is the treatment carried out?
First, a doctor must obtain a tumor fragment with a diameter of at least 2 cm. An excision biopsy is used for this purpose. In fact, minor surgery is performed, during which, the doctors receive the required amount of tissue.
The tumor is dissected into fragments of 1 to 3 cubic millimeters. They are cultivated for several weeks, and then interleukin-2 is added. Although many cancer cells are present in the material at the time of its harvesting, all of them gradually die "by their own death" or are destroyed by lymphocytes.
The cultivation period lasts 2-4 weeks. Then, TIL is tested for reactivity to tumor cells. Namely, the doctors verify whether these lymphocytes can destroy the melanoma in a particular patient. All of the tissues are cultivated in different tubes. The doctors check which populations of immune cells are more successful in fighting the tumor. The specialists continue to multiply the most aggressive samples in order to obtain as many cells as possible. They cultivate them for another 2 weeks.
In total, the cultivation phase lasts 5-6 weeks. At the first stage, the doctors obtain 30-50 million cells. Then, during the final 2 weeks, their number is brought up to 1 billion. This is the minimum required for a successful treatment. Subsequently, these billion cells, or a little more, are injected into the patient's body.
Is it always possible to obtain cells for the treatment of melanoma?
The doctors do not always manage to obtain a generation of cells which are aggressive enough against the tumor. On average, they obtain them with a probability of 60 to 90%.
The researchers have demonstrated that the chance of success mostly depends on the age of the patient. In people under 30 years old, the chance of successfully receiving TIL is 94%, while for patients older than 60 years old, it is only 46%. Cells can be obtained more often in women than in men. People who underwent the chemotherapy course more than 3 months ago, have a better chance of receiving a good population of cells.
The results
Good treatment results can be achieved in 50% of patients. Their symptoms are less severe, most tumor foci regress, the growth rate of the tumor slows down, and the duration and quality of life increase. In 20% of patients the tumor and its metastases regress completely.
Although TIL therapy does not guarantee a cure, even the above mentioned results should be considered impressive. After all, do not forget which patients can be treated using immunotherapy. These are mainly people with an advanced stage of the disease, who no longer receive any results from other treatment methods. That is, doctors manage to achieve excellent results, even in the most severe cases.
It is worth mentioning the disadvantages of TIL protocol, which at the moment do not allow doctors to make the technique a standard method for the treatment of melanoma at its advanced stages. It has two main disadvantages, such as:
- high price;
- significant duration – up to 6 weeks.
Not all patients can pay for TIL. This type of therapy is not available in all countries. It is carried out only in highly specialized cancer centers. Patients with the most aggressive types of melanoma are not always able to wait 5-6 weeks until the population of immune cells is ready. Therefore, not every patient is a candidate for this treatment technique.
Enhanced protocols
Doctors constantly develop new, improved TIL protocols. They strive to make the treatment more effective, safer, and accessible, so that patients can get it faster.
The main immunotherapy options for metastatic melanoma using TIL, which are already used in clinical practice or at the research phase, are the following ones:
- Low doses of interleukin-2 – some trials demonstrate that such treatment can reduce side effects with comparable results
- Young-TIL – treatment protocol, which has a shorter duration (allows patients with a rapidly progressing melanoma to undergo the treatment)
- Immunosuppressive medications and total body irradiation – increase the effectiveness of TIL
- Increasing doses of drugs, which suppress immunity – in some trials a frequency of complete responses to immunotherapy up to 40% was demonstrated (but such treatment regimens have more side effects)
- The possibility of using interleukin-15 and interleukin-21 instead of, or in addition to, the traditionally used interleukin-2 is studied
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Is the treatment safe?
Most side effects are caused by chemotherapy, which is used during TIL. The main ones are:
- gastrointestinal discomfort;
- fatigability;
- lower blood cell count.
Blood transfusions are required in many patients. A decrease in the number of immune cells increases the risk of infections. If they occur, antibiotics are used. During the treatment of infectious pathologies, TIL cells can be stored frozen.
Immediately after the intravenous administration of TIL, most patients experience chills and a fever. Many patients have an increased heart rate and high blood pressure.
How can I get TIL therapy?
You can use the services of Booking Health to check the average cost of treatment and information about specialized medical centers. We will arrange treatment abroad for you. We offer the following benefits:
- Selection of the best clinic, which specializes in immunotherapy for melanoma, uses the TIL protocol, and has the best statistics for therapy results
- Reduced waiting for treatment, which is especially important in rapidly progressive metastatic melanoma
- Reduced costs for treatment – costs will be reduced due to avoiding additional coefficients for foreign patients
- Direct communication with the doctor who will carry out your immunotherapy for melanoma
- Preparation of a treatment program without repeating previously performed diagnostic tests
- Buying and forwarding of medicines
- Communication with the clinic after the treatment program is complete
- Organization of additional diagnostics, treatment, or rehabilitation
The specialists at Booking Health ensure high-quality services. We will book your hotel and airline tickets for you, meet you at the airport, and take you to the hospital by car.
Choose treatment abroad and you will for sure get the best results!
Authors:
The article was edited by medical experts, board certified doctors Dr. Nadezhda Ivanisova, Alexandra Solovey. 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:
New England Journal of Medicine
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