Glioblastoma is a highly malignant brain tumor (WHO grade IV) characterized by infiltrative growth and a high risk of recurrence. Standard treatment methods often fail to provide long-term disease control due to the tumor’s growth pattern, anatomical location, and limited ability to deliver therapeutic agents into brain tissue. Immunotherapy is typically applied after surgery or in cases of recurrence as part of an individualized treatment strategy and may include oncolytic viruses, therapy delivery via an Ommaya reservoir, and ATACK cellular immunotherapy.
Limitations of Standard Glioblastoma Treatment Methods
Surgery
Surgical removal of the tumor is one of the main stages of glioblastoma treatment. However, even after resection of the visible tumor mass, cancer cells frequently remain beyond surgical margins, are not detected by standard imaging techniques, and may subsequently lead to disease recurrence. Repeated surgical interventions are associated with an increased risk of neurological complications and are not always feasible.
Radiation Therapy
Radiation therapy is widely used in glioblastoma to control tumor growth and may result in a reduction in tumor volume. However, even with modern high-precision radiation techniques, surrounding healthy brain tissue is inevitably affected. In addition, radioresistant glioblastoma cells may persist after treatment, contributing to disease recurrence.
Chemotherapy
The effectiveness of chemotherapy in glioblastoma is limited by poor penetration of most agents through the blood–brain barrier. Furthermore, glioblastomas—particularly those with an unmethylated MGMT promoter—often demonstrate reduced sensitivity to temozolomide, which limits the long-term effectiveness of standard chemotherapy.
Why Glioblastoma Is Difficult to Treat
Glioblastoma responds poorly to treatment due to a combination of several factors. Tumor cells diffusely infiltrate brain tissue, including functionally critical areas, which often makes complete surgical removal impossible. Additionally, the blood–brain barrier (BBB) restricts the penetration of most systemic drugs into brain tissue. The combination of these factors, together with the highly malignant nature of the tumor, significantly reduces the effectiveness of standard treatment approaches.
Why Immunotherapy Is Used for Glioblastoma
Standard treatment approaches are primarily aimed at reducing tumor mass and generally do not eliminate infiltrative glioblastoma cells at resection margins or along white matter tracts. Therefore, long-term disease control requires therapeutic strategies capable of targeting residual tumor cells with involvement of the immune system.
Immunotherapy for brain cancer is not used as a replacement for standard treatment, but rather as a complementary strategy designed to overcome the biological limitations of surgery, radiation therapy, and chemotherapy. It enables activation of the immune system to recognize and suppress tumor cells, including those located in regions inaccessible to local treatment methods. Some immunotherapeutic approaches can act directly within brain tissue or partially bypass the blood–brain barrier.
Minimal Residual Disease
Minimal residual disease (MRD) refers to malignant cells that remain in the body after surgery, radiation therapy, or chemotherapy but are not detectable by MRI or PET-CT.
The period of minimal residual disease is considered an optimal clinical window for immunotherapy, as tumor burden is minimal and achieving a comparable degree of tumor reduction later may be unattainable.
Glioblastoma Immunotherapy Methods
Our glioblastoma treatment program integrates several immunotherapy approaches that are applied in combination and complement one another. This strategy is considered after completion of 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 the treatment of aggressive brain tumors.
Oncolytic Viruses
Oncolytic viruses are viral strains that are safe for humans and genetically modified to selectively infect and destroy cancer cells. Their therapeutic effect is based on several complementary mechanisms.
During treatment, oncolytic viruses:
directly destroy glioblastoma cells through viral replication within tumor cells, followed by spread of the virus to neighboring malignant cells
promote the release of tumor antigens, making cancer cells more recognizable to the patient’s immune system
convert immunologically “cold” glioblastoma tumors into an immunologically active state, rendering them accessible to an antitumor immune response
create a localized inflammatory environment within the tumor, enhancing the effectiveness of subsequent immunotherapeutic approaches
Oncolytic viruses for glioblastoma may be administered via different routes depending on the clinical situation and tumor localization:
intravenous administration
intranasal administration
direct intratumoral or intracavitary administration via an Ommaya reservoir
Checkpoint Inhibitors
Oncolytic viruses are used in glioblastoma treatment not only for direct tumor cell destruction, but also to render the tumor visible to the immune system. Following viral therapy, tumor antigens become recognizable; however, the resulting antitumor immune response may remain insufficiently active.
Checkpoint inhibitors are typically applied at a subsequent stage to remove inhibitory signals that prevent the immune system from mounting an effective attack against the tumor. This sequential approach allows oncolytic viruses to exert their therapeutic effect first, after which the immune response can be enhanced without prematurely suppressing viral activity.
Anti-Cancer Vaccines
Anti-cancer vaccines represent another immunotherapeutic approach for glioblastoma, aimed at training the patient’s immune system to recognize tumor cells. Vaccination induces an immune response against tumor-specific antigens, helping the immune system distinguish malignant cells from healthy tissue.
Each vaccine is produced individually for a specific patient using tumor material obtained during surgical resection. This personalized approach allows for consideration of the unique biological characteristics of each tumor.
Ommaya Reservoir: Direct Therapy Delivery for Glioblastoma
The Ommaya reservoir is an implantable access system that enables direct administration of therapeutic agents into the brain or tumor cavity.
This approach is particularly relevant in clinical situations where direct delivery of therapy to the tumor is required and systemic treatment methods are insufficient.
The Ommaya reservoir allows:
bypassing the blood–brain barrier
direct administration of therapy into the postoperative cavity
repeated administrations without the need for additional surgical intervention
ATACK Therapy: Donor Lymphocyte Treatment
ATACK therapy is a form of cellular immunotherapy used to eliminate residual malignant cells after tumor reduction.
ATACK therapy utilizes activated donor lymphocytes capable of recognizing and destroying cancer cells. In patients with cancer, prolonged disease course and prior treatments often lead to immune exhaustion, reducing the antitumor capacity of the patient’s own immune system. Donor lymphocytes retain higher functional activity and effectiveness compared with autologous immune cells. ATACK therapy is typically applied after maximal tumor reduction, preferably during the stage of minimal residual disease (MRD).
For individualized selection of cellular immunotherapy, we recommend testing tumor tissue for expression of key antigens (HER2/neu, PD-L1, EGFR, VEGF, TROP-2, GD2, HIF-2α, c-KIT, PDGFR).
Individualized Treatment Protocol
Each immunotherapy protocol for glioblastoma is developed individually. Treatment may involve oncolytic virus therapy alone or in sequential combination with ATACK therapy. Protocol design is based on tumor biology, molecular characteristics, and estimated risk of recurrence.
In Which Cases Can Immunotherapy Be Recommended for Glioblastoma?
An individualized immunotherapy protocol may be recommended for patients who:
have a diagnosis of glioblastoma (WHO grade IV)
have residual tumor tissue after surgery
experience glioblastoma recurrence
have exhausted standard treatment options
How We Evaluate Each Case
Preliminary evaluation includes:
detailed review of all prior treatments
analysis of MRI scans
histological and molecular tumor data
assessment of the patient’s clinical condition and feasibility of travel for treatment
How Does Glioblastoma Treatment Proceed?
Following an online consultation and protocol development, comprehensive glioblastoma immunotherapy is initiated at partner clinics in Germany or Kazakhstan.
Treatment may include oncolytic virus therapy, ATACK therapy, photodynamic therapy (PDT), and supportive immunomodulatory approaches.
MRI-based monitoring is used to evaluate treatment response and guide further clinical decisions.
Support for International Patients
We support patients at all stages of brain cancer treatment abroad, including:
coordination with clinics and treatment planning
assistance with travel preparation and logistical arrangements
remote medical follow-up after return home
communication with local treating physicians when necessary
What to Expect from Treatment
Potential goals of glioblastoma immunotherapy include:
disease stabilization
slowing of disease progression
reduction of recurrence risk
preservation of neurological function and quality of life
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