Astrocytoma is a brain tumor that develops from cells called astrocytes. According to the World Health Organization classification, astrocytomas range from grade I (least malignant) to grade IV. Standard treatment methods often fail to provide long-term disease control in high-grade astrocytomas due to infiltrative tumor growth, tumor location, and limited delivery of therapy to brain tissue. Immunotherapy is applied after surgery or in recurrence as part of an individualized strategy and may include oncolytic viruses, therapy delivery through an Ommaya reservoir, and ATACK cellular immunotherapy.
Astrocytomas are classified by grade of malignancy and molecular markers:
Grade I malignancy: Pilocytic astrocytoma is a slow-growing tumor that most commonly develops in the cerebellum and, as a rule, does not infiltrate the surrounding brain tissue.
Grade II malignancy: Diffuse astrocytoma is a tumor with infiltrative growth that can gradually spread into surrounding brain tissue and may progress over time.
Grade III malignancy (previously anaplastic astrocytoma): A more aggressive form of the disease, characterized by faster growth and more pronounced involvement of healthy brain tissue.
Grade IV malignancy: The most aggressive form, characterized by rapid growth and a high risk of progression. In the current WHO classification of 2021, grade IV tumors are subdivided based on molecular features into astrocytoma with an IDH mutation Grade 4 and glioblastoma, which refers only to tumors without an IDH mutation.
Limitations of Standard Astrocytoma Treatment Methods
Surgery
For pilocytic astrocytoma (grade I), active surveillance with regular MRI monitoring is often possible in the absence of symptoms and tumor growth. For grade II–IV astrocytomas, the tumor is characterized by infiltrative growth and increased risk of progression, so surgical intervention often represents an important stage of treatment if the location and size allow the operation to be performed safely.
However, complete tumor removal is not always possible: difficult-to-access location or large tumor masses create a risk of damage to vital brain centers. Such intervention may lead to disability (speech impairment, paralysis) or significantly reduce quality of life. Repeat surgical interventions are associated with an even higher risk of complications.
Even after removal of tumor tissue in high-grade astrocytomas, cancer cells often remain beyond surgical margins and may subsequently lead to disease recurrence.
Radiation Therapy
Radiation therapy is used for astrocytomas to control tumor growth and may lead to reduction in its volume. However, radiation affects not only malignant but also healthy cells. This can cause damage to brain tissue and development of cognitive impairments, as well as other side effects. In addition, astrocytoma cells with resistance to radiation may persist after treatment, which contributes to disease recurrence.
Chemotherapy
For grade II–IV astrocytomas after surgery, chemotherapy is often considered as part of a multimodal treatment approach. The choice of drugs and duration of therapy depend on the biological characteristics of the tumor and the patient’s condition. The effectiveness of chemotherapy for astrocytomas is limited by poor penetration of most drugs through the blood-brain barrier. In addition, tumor cells may become resistant to conventional treatment methods, which reduces the long-term effectiveness of standard chemotherapy.
Why High-Grade Astrocytomas Are Difficult to Treat
Grade II-IV astrocytomas often respond poorly to standard treatment due to a combination of several factors. Tumor cells spread diffusely into brain tissue, penetrating functionally important areas, which often makes complete surgical removal impossible. Additionally, the blood-brain barrier limits the penetration of most systemic drugs into brain tissue. The combination of these factors significantly reduces the effectiveness of standard treatment methods.
A recurrence can develop even from a single malignant cell remaining in the body after treatment.
Why Immunotherapy Is Used for Astrocytoma
Standard methods are aimed at reducing tumor mass but do not eliminate infiltrative astrocytoma cells at resection margins or along white matter tracts. Long-term disease control requires strategies capable of targeting residual tumor cells through immune system engagement.
Immunotherapy for brain cancer is used not as a replacement for standard treatment, but rather as a complementary strategy. After application of conventional methods, there is an opportunity to convert cancer to a stage of minimal residual disease, when a small number of cancer cells remain in the body. Immunotherapy engages the immune system in recognizing and suppressing the tumor process, including in zones inaccessible to local treatment methods. Some immunotherapeutic approaches are capable of acting directly in brain tissues or partially bypassing the blood-brain barrier (BBB).
Immunotherapy Methods for Astrocytoma
Our astrocytoma treatment program combines several immunotherapy methods that are applied in combination and complement each other. This approach is considered after standard treatment and in cases of recurrence. All treatment protocols are developed individually and are based on many years of clinical and research experience in treating aggressive brain tumors.
Oncolytic Viruses
Oncolytic viruses are viral strains safe for humans, modified in such a way as to selectively infect and destroy cancer cells. Their therapeutic action is based on a combination of several complementary mechanisms.
During treatment, oncolytic viruses:
- directly destroy astrocytoma cells through viral replication inside tumor cells with subsequent spread of the virus to neighboring cancer cells
- promote the release of tumor antigens, making cancer cells more recognizable to the patient’s immune system
- convert immunologically “cold” tumors into an immunologically active state in which they become accessible to an antitumor immune response
- form a local inflammatory environment inside the tumor, enhancing the effectiveness of subsequent immunotherapeutic approaches
Oncolytic viruses for astrocytoma can be administered in various ways depending on the clinical situation and tumor location:
- intravenous administration
- intranasal administration
- direct intratumoral or intracavitary administration through an Ommaya reservoir
Direct introduction of oncolytic viruses into the tumor allows achieving maximum effect: without the need to overcome the blood-brain barrier of the brain, and the viruses will be able to act on the tumor directly. This procedure can be performed directly during the operation to remove the astrocytoma or using an Ommaya reservoir.
Checkpoint Inhibitors
Oncolytic viruses are used in astrocytoma treatment not only for direct destruction of tumor cells, but also to make the tumor recognizable to the immune system. After viral therapy, the immune system begins to see tumor antigens, however the antitumor immune response may remain insufficiently active.
Checkpoint inhibitors are usually applied at the next stage to remove limitations that prevent the immune system from fully attacking the tumor. Such a sequential approach allows oncolytic viruses to carry out their action, after which the immune response can be enhanced without premature suppression of viral activity.
Anti-Cancer Vaccines
Anti-cancer vaccines are one approach to astrocytoma immunotherapy aimed at teaching the patient’s immune system to recognize tumor cells. The vaccine forms an immune response against specific tumor antigens, helping the immune system distinguish tumor cells from healthy tissues.
Each vaccine is manufactured individually for a specific patient using tumor material obtained during surgical removal of the tumor. Such a personalized approach allows taking into account the characteristics of a specific tumor. To make such treatment possible, we recommend cryopreserving a sample of the tumor tissue in our Tumor Bank.
Ommaya Reservoir: Direct Therapy Delivery for Astrocytoma
The Ommaya reservoir is an implantable access system that allows introducing therapeutic drugs directly into the brain or into the tumor cavity.
The Ommaya reservoir allows:
- bypassing the blood-brain barrier
- introducing therapy directly into the postoperative cavity
- performing repeated administrations without additional surgical intervention
ATACK Therapy: Treatment with Donor Lymphocytes
ATACK therapy is a method of cellular immunotherapy used to destroy remaining malignant cells after tumor reduction. The method uses activated donor lymphocytes capable of recognizing and destroying cancer cells. In cancer, prolonged disease and previous treatment often deplete the patient’s immune system, reducing its antitumor potential. Donor lymphocytes retain higher activity and effectiveness compared to the body’s own immune system cells. ATACK therapy is usually applied after maximum tumor reduction, preferably at the stage of minimal residual disease (MRD).
What Is Minimal Residual Disease
Minimal residual disease (MRD) is cancer cells that remain in the body after surgery, radiation, or chemotherapy but are not detected by MRI or PET-CT.
The period of minimal residual disease is considered the optimal clinical moment for immunotherapy, since the tumor burden is minimal and subsequent equally pronounced tumor reduction may be unachievable.
Individual Treatment Protocol
The immunotherapy protocol for astrocytoma is developed individually for each patient. Treatment may include oncolytic virus therapy alone or in sequential combination with ATACK therapy. Protocol design depends on the grade of malignancy of the astrocytoma, tumor biology, molecular characteristics, and risk of recurrence. For individual selection of immunotherapy, we recommend testing the tumor for expression of key antigens (HER2/neu, PD-L1, EGFR, VEGF, TROP-2, GD2, HIF-2α, c-KIT, PDGFR).
In Which Cases May Immunotherapy Be Recommended for Astrocytoma
An individual immunotherapy protocol may be recommended for patients who:
- have diagnosed grade II-IV astrocytoma
- have residual tumor tissue after surgery
- have encountered astrocytoma recurrence
- have exhausted standard treatment methods
How We Evaluate Each Case
Preliminary evaluation includes:
- detailed analysis of all previously performed treatment methods
- examination of MRI images
- histological and molecular data
- assessment of clinical condition and ability to travel for treatment
How Treatment for Astrocytoma Proceeds
After an online consultation and protocol development, comprehensive astrocytoma immunotherapy begins in partner clinics in Germany or Kazakhstan.
Treatment may include oncolytic virus therapy, ATACK therapy, photodynamic therapy (PDT), and supportive immunomodulating approaches.
MRI-based monitoring is used to assess response to treatment and determine further steps.
Support for International Patients
We accompany patients at all stages of brain cancer treatment abroad, including:
- organizing interaction with clinics and coordinating treatment
- assistance with travel preparation and resolving organizational issues
- remote medical monitoring after returning home
- if necessary — interaction with treating physicians at the patient’s place of residence
What Results Can Be Expected from Treatment
Potential goals of astrocytoma immunotherapy include:
- disease stabilization
- slowing of progression
- reduction of recurrence risk
- preservation of neurological functions and quality of life
- in individual cases — long-term disease control for low- and intermediate-grade malignancies
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