Dendritic cell vaccines: treatment of brain tumors

Currently, the most effective standard treatment for malignant brain tumors is surgery followed by radiation and/or chemotherapy. Unfortunately, this approach does not achieve a significant improvement in clinical outcome.

For glioblastoma (one of the most aggressive forms of brain cancer), conventional treatment provides a median survival of 15 months. However, only 5% of patients survive more than 2 years. Thus, there is an urgent need for new less toxic and more effective treatments. And cancer vaccination has become one of them.

Dendritic cell vaccines in neurooncology

Immunotherapy of neurooncological diseases is a rapidly developing branch of experimental and clinical oncology. Currently, scientists are paying special attention to a promising method of treatment with vaccines based on autologous (own) dendritic cells. These are the antigen-presenting cells of the body, which constitute the primary link in the immune response.

Dendritic cells capture, process and present foreign antigens to lymphocytes. Simply put, they train killer cells to recognize potential dangers. Although dendritic cells account for approximately 0.3% of all circulating white blood cells, they serve as guardians of the immune system and are found in a wide variety of parts of the body.

Information from Medtour!For the discovery of dendritic cells and their functions, American cytologist and immunologist Ralph Steinman was awarded the Nobel Prize in Medicine in 2011.

Dendritic cell vaccine for brain cancer: what do the studies say?

The first study on the research of a dendritic cell vaccine in the treatment of glioma was conducted by Swedish scientists in 1996. Rats with intracranial gliomas were injected with spleen-derived dendritic cells mixed with irradiated glioma cells. After four subcutaneous vaccinations, which were performed 2 weeks apart, the survival rate of the rats improved significantly. Some rodents recovered completely. At the same time, all control animals died within 40 days. Immunized rats were alive 200 days after vaccination.

In the late 1990s, American neurosurgeon and neuroscientist Linda Liau and her team became the first to test a dendritic cell vaccine in patients with glioblastoma. Previously, this tumor was considered immunoprivileged, that is, the immune system could not attack it. However, Liau and colleagues were able to demonstrate that the body can indeed mount an immune response against tumors in the brain after vaccination.

In the following years, numerous scientific experiments were carried out on animals and humans. Their results are difficult to compare due to differences in study design. However, scientists were able to draw several important conclusions:

• Dendritic cell vaccines are safe in the treatment of brain tumors.
• Immunotherapy with dendritic cells can lead to a significant increase in the survival of laboratory animals and patients with gliomas. In the case of a study involving rats, there were cases of complete cure.
• Vaccination with dendritic cells leads to long-term immunity (prevention of tumor recurrence).

The latest and largest study to date, conducted by scientists at the University of California, Los Angeles, showed impressive results. Patients with glioblastoma received the cancer vaccine at 80 centers worldwide from 2007 to 2015. Prior to the trial, each participant underwent surgery to remove a tumor, followed by chemotherapy and radiation.

Nearly 30% of the patients in the study survived at least three years after the start of the experimental treatment. For comparison, the current average life expectancy for patients diagnosed with glioblastoma is 15–17 months. Less than 5% of people receiving standard care survive more than 5 years after diagnosis.

Brain tumor vaccine safety and tolerability study

Five publications reported no toxicity of dendritic cell vaccine therapy. A total of 399 adverse events were reported, not counting the expected minor reaction at the injection site. The most common side effect was fatigue, which was observed in 11% of patients included in the trials. Thus, dendritic cell vaccination can be considered a safe and well tolerated treatment for brain tumors.

Study of the quality of life of vaccinated patients

In two studies that used the Karnovsky scale (index of cancer patient status), the median KPS was higher in patients treated with dendritic cell vaccine than in patients in the control group. Another study found that vaccinated patients were more functionally independent than control patients.

Treatment of glioma with dendritic cell vaccine

Gliomas are the most common type of malignant brain tumors. One of the most aggressive forms of gliomas is glioblastoma (grade 4 astrocytoma). This is a rapidly growing tumor that is extremely difficult to treat with standard methods such as chemotherapy and radiotherapy.

Since glioblastoma infiltrates the brain tissue, it is almost impossible to completely remove it surgically. Because of this, in most cases, after surgery, the tumor recurs. Dendritic cell vaccines allow the body to fight the tumor by activating the patient’s own immune system. According to available data, vaccination with dendritic cells can increase the 5-year survival rate of patients from 5% to 20%.

Treatment of anaplastic astrocytoma with dendritic cell vaccine

Astrocytomas are tumors arising from astrocytes (neuroglial cells). These are the most common brain tumors in adult patients. Anaplastic astrocytoma is a tumor without clear boundaries that grows into the brain tissue. It is difficult to treat with surgery, chemotherapy and radiation.

The experience of foreign oncologists shows that the use of anti-cancer dendritic cell vaccines can increase the life expectancy of patients with stage 3 astrocytoma by almost 2 times. An additional advantage of this type of treatment is good tolerability. Approximately 80% of patients do not experience serious side effects.

Treatment of anaplastic oligodendroglioma with dendritic cell vaccine

Oligodendroglioma is a tumor that most often occurs in the white matter or cerebral cortex. Neoplasms of the 2nd degree of malignancy (anaplastic oligodendrogliomas) grow rapidly and are quite aggressive.

The use of dendritic cell vaccines can stop the growth of the tumor, and in some patients even leads to its reduction. In addition, vaccine therapy improves the quality of life of cancer patients. According to Belgian scientists, 6 out of 7 patients treated with dendritic cells are satisfied with their physical condition and are able to lead a full life.

Advantages of dendritic cell vaccines in the treatment of brain tumors

Cancer vaccines offer hope for patients with aggressive tumors such as glioblastomas or anaplastic astrocytomas. This treatment method has a number of advantages:

• Minimal discomfort. Dendritic cell therapy is comparable to conventional vaccination. Patients experience only minor discomfort during the collection of blood cells and during the administration of the vaccine.
• Absence of severe side effects. Most patients receiving vaccine therapy experience minimal adverse reactions. This may include itching or a slight burning sensation at the injection site, as well as fatigue that goes away with time.
• Efficiency. Studies have shown that the use of dendritic cell vaccines can significantly increase the life expectancy of patients with brain tumors.
• Compatibility with other methods of treatment. Vaccination is usually carried out as part of the standard treatment (surgery + chemotherapy + radiotherapy). The use of dendritic cells makes it possible to increase the effectiveness of traditional methods of treatment.

Sources of:    aacrjournals.orgcancerres thebraintumourcharity.org onclive.com cancer.gov dovepress.comindex.php mayoclinic.org molmed.biomedcentral.com