Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all diagnosed breast cancer cases and is considered one of the more biologically more aggressive subtypes, with limited options for targeted therapy.
The defining characteristic of triple-negative breast cancer is the absence of three key markers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
The absence of these receptors makes this tumor subtype less responsive to hormonal therapy and HER2-targeted agents used in other forms of breast cancer. As a result, treatment of triple-negative breast cancer is in most cases based on chemotherapy, and the clinical course is often characterized by a more aggressive clinical course and an increased risk of early recurrence.
Immunotherapy for Triple-Negative Breast Cancer
Immunotherapy is considered one of the systemic treatment directions in triple-negative breast cancer. This tumor subtype is in some cases characterized by elevated immunogenicity, the presence of tumor-infiltrating lymphocytes (TILs), and possible PD-L1 expression, factors that may influence sensitivity to immune-based strategies.
The immunotherapy approach is determined individually based on the molecular characteristics of the tumor, the extent of disease, prior treatment, and the patient’s clinical condition.
In addition to approved immunological agents, an individualized protocol may incorporate further immunotherapy methods aimed at engaging the immune system in the recognition and elimination of tumor cells.
Oncolytic Virus Therapy
Oncolytic virus therapy is one of the key components of the immunotherapeutic approach to triple-negative breast cancer. Oncolytic viruses selectively target and replicate within tumor cells, using their intracellular mechanisms, a process may lead to the death of the infected cell. Released viral particles then enter neighboring tumor cells, sustaining localized anti-tumor activity within the tumor site.
Through this process, oncolytic virus therapy can directly damage and destroy tumor cells, trigger the release of tumor antigens, engage the immune system in recognizing cancer cells, and generate a local inflammatory response that enhances the effect of subsequent treatment stages.
Depending on clinical indications, the method may be combined with direct intratumoral virus injection or integrated with other therapeutic approaches within a comprehensive treatment plan.
Checkpoint Inhibitor Therapy
Tumor cells evade immune recognition in two ways: by reducing their own visibility to the immune system, or by actively suppressing the immune response through regulatory mechanisms known as immune checkpoints. Oncolytic virus therapy addresses the first of these mechanisms. Infected tumor cells acquire viral antigens that the immune system recognizes as foreign, making them visible targets for immune attack.
Checkpoint inhibitors target the second mechanism. Under normal conditions, immune checkpoints protect the body’s own tissues from autoimmune reactions; however, tumor cells exploit this same pathway to weaken the anti-tumor immune response. Checkpoint inhibitors block this suppression and help restore the ability of immune cells to attack the tumor.
Following completion of the oncolytic virus therapy course, checkpoint inhibitors are considered as the next stage of treatment. This sequence reflects the specifics of their immune action: activating the immune response too early, while the virus is still working, can reduce its effectiveness. In this two-stage approach, viral therapy makes the tumor visible to the immune system, while checkpoint inhibitors remove the suppressive protection that the tumor has established.
In cases of intolerance or unavailability of checkpoint inhibitors, cytokine-mediated immunotherapy may be considered as an alternative.
Individualized Anti-Cancer Vaccines
When cryopreserved tumor tissue is available, a personalized anti-cancer vaccine can be prepared based on the patient’s own tumor material. Unlike preventive vaccines against infections, these vaccines are designed to train the immune system to recognize and attack the specific tumor cells of a given patient.
The patient’s tumor material undergoes specialized laboratory processing and is then administered as an immunological stimulus. This approach may help enhance immune recognition of tumor cells that were previously less visible to the immune system.
Preparation of a personalized vaccine requires a tumor tissue sample obtained through biopsy or surgical intervention and preserved by cryopreservation.
ATACK: Donor Lymphocyte Therapy
ATACK (Allogeneic Targeted Activated Cancer Killer cells) is a method of cellular immunotherapy that uses specially prepared donor immune cells (such as T cells and NK cells), for targeted action against tumor cells. The key principle of the method is the use of donor cells that are intentionally different from the patient’s own cells. This difference allows them to recognize cancer cells as foreign and trigger a more pronounced immune elimination response.
To enhance targeting specificity, monoclonal antibodies directed against antigens expressed on the surface of tumor cells may be applied.
ATACK may be considered within an individualized treatment protocol, particularly in the setting of minimal residual disease (MRD), when the primary tumor burden has been reduced and the therapeutic strategy is focused on controlling remaining tumor cells.
Photodynamic Therapy
Photodynamic therapy (PDT) may be integrated into a comprehensive immunotherapeutic approach as a method of both direct tumor destruction and immune activation. PDT uses photosensitizers that selectively accumulate in tumor cells and are activated by light of a specific wavelength, generating reactive oxygen species that damage cancer cells.
Combined use of PDT can contribute to local destruction of tumor foci, stimulate a local immune response, and enhance the activity of other immunotherapy components, including oncolytic viruses. Depending on the clinical situation, PDT may be applied locally or as part of a combined therapeutic approach.
Who May Be Considered for Immunotherapy in Metastatic Triple-Negative Breast Cancer?
Immunotherapy for metastatic triple-negative breast cancer may be considered for patients who:
- have not achieved a clinically meaningful response to standard treatment approaches for metastatic triple-negative breast cancer;
- are exploring additional therapeutic options after completion of standard therapy;
- have the ability to travel abroad to receive specialized treatment.
Depending on the individual characteristics of the disease, specific immunotherapy methods may be considered in the presence of the following factors:
- tumor lesions that are potentially accessible for direct therapeutic intervention, when clinically justified;
- tumor material (fresh or cryopreserved) that, in selected cases, may be used for the development of a personalized anti-cancer vaccine.
How Each Case Is Evaluated
The preliminary assessment of the possibility of immunotherapy for metastatic breast cancer includes:
- a detailed analysis of previously administered treatment methods and their outcomes;
- review of imaging data (MRI, CT, PET-CT) to assess the extent and localization of the disease;
- evaluation of molecular and genetic testing results or recommendations for additional testing when necessary.
How Treatment Is Conducted
Immunotherapy programs for metastatic breast cancer generally include the following stages:
- an individual online consultation with Professor Shimon Slavin;
- treatment planning and development of a personalized therapeutic protocol;
- implementation of specialized immunotherapeutic procedures in partner clinics in accordance with local regulatory requirements;
- application of additional immunotherapy methods when medically indicated;
- in-person and remote patient follow-up and support.
Treatment involves coordination among several specialized medical centers to ensure a comprehensive and integrated approach.
International Patient Support
For patients traveling from other countries to receive treatment, the following support is provided:
- guidance and assistance throughout all stages of international treatment;
- support with medical travel arrangements;
- remote follow-up and support after returning home;
- coordination with local treating physicians for continued monitoring.
Next Steps
To determine whether immunotherapy for metastatic breast cancer may be considered in your case:
- complete the contact form on the website;
- submit medical records for preliminary review;
- schedule an individual consultation.
Each clinical case is reviewed on an individual basis. Immunotherapy programs for metastatic breast cancer may be of interest to patients who have already undergone standard treatment stages and are exploring additional therapeutic options.
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