Brain Cancer Immunotherapy

Brain cancer is one of the most challenging malignancies to treat due to the blood-brain barrier, which prevents most drugs from reaching the brain, and the high risk of recurrence even after intensive therapy. Immunotherapy for brain cancer aims to activate the immune system to recognize and eliminate cancer cells that may persist after surgery, radiation therapy, or chemotherapy.

At Biotherapy International, we develop individualized immunotherapy protocols for patients with brain cancer — primarily in the post-surgical period and in cases of recurrence, when standard treatment options are often limited.

Limitations of Standard Brain Cancer Treatments

Surgery

Surgical removal of the tumor is one of the primary treatment methods for brain cancer. However, complete resection is often not possible due to the tumor’s proximity to vital brain structures. In addition, repeat surgical procedures significantly increase the risk of neurological complications and may negatively affect the patient’s quality of life.

Radiation Therapy

Radiation therapy is widely used to control tumor growth and may lead to a reduction in tumor size. At the same time, radiation affects not only tumor tissue but also healthy brain tissue. Even after completion of a radiation course, residual cancer cells may persist and contribute to disease recurrence.

Chemotherapy

The effectiveness of chemotherapy in brain tumors is limited by the poor penetration of most drugs through the blood–brain barrier. In addition, glioblastomas with an unmethylated MGMT status often demonstrate limited sensitivity to temozolomide. Chemotherapy may also suppress immune function, reducing the body’s ability to control the disease.

Why Immunotherapy Is Used in Brain Cancer

Immunotherapy for brain cancer is primarily considered in situations where standard treatments do not fully eliminate malignant cells. After surgery, radiation, or chemotherapy, residual cancer cells may remain undetectable by imaging and contribute to tumor recurrence.

Immunotherapy is designed to target these residual and treatment-resistant cells by supporting immune recognition of tumor-specific antigens. Certain immunotherapy approaches can act locally within the brain or partially bypass the blood–brain barrier, which limits the effectiveness of many systemic drugs.

For this reason, immunotherapy is most commonly used after tumor reduction or in cases of recurrent disease, as part of an individualized treatment strategy.

Minimal Residual Disease (MRD)

Minimal residual disease refers to cancer cells that remain in the body after surgery, radiation therapy, or chemotherapy but are not detected on MRI or PET-CT scans. MRD is one of the main causes of recurrence and is considered a key target for immunotherapy.

Immunotherapy Approaches for Brain Cancer

Our brain cancer treatment program combines several immunotherapy methods that are used together and complement one another. This approach is considered in cases where the disease is resistant to standard treatments or when there is a high risk of recurrence. All treatment protocols are developed on an individual basis and are grounded in clinical and research experience accumulated over many years of working with patients with brain tumors.

Oncolytic Virus Therapy

bOncolytic viruses selectively infect and destroy malignant brain tumor cells while largely sparing healthy tissue.

The effect of oncolytic viruses is based on several complementary mechanisms. During treatment, they:

• directly destroy cancer cells through viral replication inside malignant cells
• promote the release of tumor-related signals, helping the immune system recognize cancer cells that were previously not detected
• convert immunologically “cold” tumors into “hot” tumors, making them more responsive to immune activity
• create a localized inflammatory environment within the tumor, which can enhance the effect of subsequent immunotherapy approaches

Unlike traditional systemic treatments, oncolytic viruses act directly within the tumor microenvironment. In brain cancer, this approach is particularly relevant for targeting residual and treatment-resistant cells after surgery or radiation therapy.

Oncolytic viruses can be administered in different ways depending on the clinical situation and tumor location. The main methods include:

• intravenous administration
• intranasal administration (through the nose)
• direct intratumoral administration via an Ommaya reservoir

Checkpoint Inhibitors

Oncolytic viruses are used in the treatment of brain cancer not only to directly destroy tumor cells, but also to make the tumor “visible” to the immune system. By breaking down cancer cells, the viruses trigger an immune reaction and help the body recognize the tumor as a target for attack. After completion of viral therapy, the immune system already “understands” what it is dealing with. However, the tumor may retain protective mechanisms that limit a full immune response.

Checkpoint inhibitors are used at the next stage of treatment. Their role is to remove this protection and lift the “brakes” that prevent the immune system from destroying the cancer cells it has already recognized. This is why checkpoint inhibitors are usually administered after oncolytic virus therapy, rather than simultaneously. A pause between these stages allows the viruses to complete their work within the tumor without being prematurely eliminated by the activated immune system.

This sequence makes it possible to first destroy part of the tumor and present it to the immune system, and then strengthen and support the anti-tumor immune response through immunotherapy.

Ommaya Reservoir: Direct Delivery of Therapy to the Brain

The Ommaya reservoir is an implanted access system that allows therapeutic agents to be administered directly into the brain or into the tumor area. This method is used in situations where systemic treatment approaches are limited by the blood–brain barrier and cannot reliably reach brain tissue or the tumor site.

The Ommaya reservoir allows clinicians to:

• bypass the blood–brain barrier and deliver therapy directly to the target area
• administer medications directly into the tumor region or the postoperative cavity
• perform repeated administrations without the need for additional surgical procedures

The Ommaya reservoir is particularly useful after surgical tumor removal, as well as in situations where treatment is aimed at minimal residual disease following chemotherapy or radiation therapy, with the goal of targeting remaining cancer cells.

ATACK Therapy: Donor Lymphocyte Treatment

ATACK therapy is a form of cellular immunotherapy used to eliminate remaining malignant cells after the main tumor mass has been reduced in patients with brain cancer.

ATACK therapy uses specially prepared donor lymphocytes that are directed to recognize and destroy cancer cells.
Over the course of a long illness and previous treatments, a patient’s own immune cells often become weakened and less effective at controlling the tumor. Donor lymphocytes have not been exposed to this prolonged stress. As a result, they retain higher activity and are able to attack remaining cancer cells more effectively.

ATACK therapy is typically applied after the primary tumor mass has been reduced through surgery, chemotherapy, radiation therapy, oncolytic virus therapy, or a combination of these methods.

This approach is particularly relevant:

• after significant tumor reduction using standard treatments
• in cases of minimal residual disease (MRD), when malignant cells remain in the body but are no longer detectable by imaging

In these situations, ATACK therapy allows targeted elimination of remaining cancer cells and helps reduce the risk of recurrence as part of an individualized treatment plan.

Individualized Treatment Protocol

Each immunotherapy protocol is developed individually.
Treatment may include oncolytic virus therapy alone or a sequential combination with ATACK therapy.

Protocol design depends on tumor type, molecular characteristics, tumor location, disease stage, and the presence of residual or recurrent disease.
The goal is to tailor treatment sequencing to the patient’s specific clinical situation.

When may immunotherapy be recommended for brain cancer

An individualized immunotherapy protocol may be recommended for patients who:

• have a diagnosed glioblastoma (WHO grade 4)
• have grade III astrocytoma or other high-grade gliomas
• have brain metastases and need additional treatment options
• have residual tumor tissue after surgery
• are experiencing disease recurrence
• have exhausted standard treatment options and are looking for additional approaches

How we evaluate each case

The preliminary evaluation includes:

• a detailed review of all previous treatments and their outcomes
• assessment of MRI scans to evaluate tumor size, location, and progression
• analysis of available tumor data, including histology and molecular-genetic profiles
• evaluation of the patient’s overall condition and ability to travel for treatment

Clinical Factors Considered in Protocol Planning

Each immunotherapy protocol is developed individually following a consultation. Treatment follows a comprehensive and, in most cases, sequential approach that may combine multiple immunotherapy methods, such as oncolytic virus therapy and ATACK therapy, depending on the clinical situation.

The treatment protocol design depends on:

• tumor type and molecular characteristics
• tumor location
• disease stage
• presence of residual or recurrent disease

How Treatment Is Performed

After an online consultation and development of an individualized protocol, comprehensive immunotherapy for brain cancer begins. Treatment is carried out in partner specialized clinics in Germany or Kazakhstan and is based on a combination of different immunotherapy approaches. These may include oncolytic virus therapy, cellular immunotherapy methods, photodynamic therapy (PDT), and other supportive immunomodulatory approaches that complement and reinforce each other.

After completion of the main treatment course, the patient remains under medical follow-up. Disease dynamics are monitored based on MRI results, and further treatment steps may be adjusted if needed.

The entire process is coordinated by the treating physicians, ensuring continuity of care at every stage.

International Patient Care

We support patients at all stages of brain cancer treatment abroad, including:

• coordination with clinics and organization of treatment
• assistance with travel preparation and logistical matters
• remote medical follow-up after returning home
• communication with the patient’s local treating physicians when needed

What to Expect From Treatment

The results of immunotherapy are individual and depend on tumor type, disease stage, and the overall clinical situation.

Potential goals of brain cancer immunotherapy include:

• disease control or stabilization
• slowing of tumor progression
• reduction of recurrence risk
• preservation of quality of life

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