Breast cancer is one of the most significant challenges in women’s health worldwide. Although advancements in treatment have improved survival rates, some subtypes, such as triple-negative breast cancer, remain particularly difficult to treat. Moreover, local recurrence and metastasis represent the greatest challenges, accounting for more than 90% of deaths related to this disease.
What is Immunotherapy?
Immunotherapy is a type of treatment that utilizes the body’s immune system to fight cancer. Its promise lies in its ability to generate durable and prolonged responses. However, when administered systemically (throughout the body), it can cause significant side effects, which limits its use.
To address these challenges, researchers are exploring an innovative option: intratumoral immunotherapy. This approach involves injecting treatments directly into the tumor, allowing for concentrated therapeutic action in the affected area and reducing side effects on the rest of the body.
How Does Intratumoral Immunotherapy Work?
Intratumoral immunotherapy not only acts directly on the tumor but can also stimulate the immune system to combat cancer cells in other parts of the body. In some cases, this approach functions as an “in situ vaccine,” activating natural defense mechanisms.
One of the highlighted treatments is the use of oncolytic viruses, such as T-VEC, which is FDA-approved for the treatment of metastatic melanoma. These viruses are genetically modified to attack cancer cells and stimulate an immune response.
Benefits of Local Immunotherapy
Concentrated Efficacy: By administering the treatment directly into the tumor, a higher concentration of the medication is achieved in the affected area.
Fewer Side Effects: This approach reduces the impact on healthy tissues, minimizing complications such as systemic immune reactions.
Immune System Activation: The therapy can activate immune cells, such as T lymphocytes, to attack cancer in both the primary tumor and metastatic areas.
Advances in Research
Clinical and preclinical studies have demonstrated promising results in the use of various agents, including:
Monoclonal Antibodies: These molecules are designed to target specific markers on cancer cells. For example, checkpoint inhibitors like pembrolizumab block signals that cancer uses to evade the immune system. Other monoclonal antibodies target specific receptors on tumor cells to directly stimulate an immune response.
Oncolytic Viruses: These modified viruses exclusively infect cancer cells, causing their destruction. They also release signals that attract immune cells to the tumor site. Examples like T-VEC have shown their ability to reduce tumors and activate the immune system in other parts of the body.
Cytokines: Cytokines are proteins that regulate communication between immune cells. Some, like interferon-alpha and interleukin-2, can strengthen the immune response against cancer. However, their systemic administration can cause significant side effects, making intratumoral application a safer and more effective alternative.
Modified Immune Cells: Cell therapies, such as CAR-T cells, are designed to identify and destroy cancer cells. These cells can be genetically modified to improve their efficacy and have shown promise in combination with intratumoral immunotherapy.
Nucleotides and Gene Therapies: DNA- or RNA-based therapies can modify tumor cell behavior or enhance immune activation. For instance, plasmids encoding cytokines or tumor antigens have been successfully used in preclinical models.
Therapeutic Bacteria: Certain modified bacteria can infect tumors, causing necrosis and stimulating an immune response at the infection site. These therapies can also act as vehicles to deliver drugs to the tumor.
Figure 1. targeted treatments are injected directly into the tumor to achieve concentrated efficacy, fewer side effects, and immune system activation. The lower section categorizes the innovative agents used in this approach, such as Monoclonal Antibodies, Oncolytic Viruses, Cytokines, Modified Immune Cells, and Gene Therapies, showcasing their roles in enhancing immune responses and directly combating cancer cells.
Challenges and Future Directions
Although intratumoral immunotherapy holds great potential, it also faces challenges. One is ensuring that the treatment is effective for a wide variety of patients and breast cancer subtypes. Additionally, researchers are working to develop delivery methods that increase the retention of the drug within the tumor and reduce discomfort associated with injections.
Another challenge is personalizing treatments according to the immune profile of each patient. This includes identifying biomarkers that predict which patients will respond best to these therapies.
For individuals diagnosed with breast cancer, these emerging therapies offer hope. While not all treatments are immediately available, advances in research are paving the way for more effective and personalized therapies.
Intratumoral immunotherapy could become a key tool in transforming how we treat breast cancer, giving patients new reasons for hope and a better quality of life.
Remember! Always consult your doctor for personalized information and to discuss the best treatment options for your situation.
Main Reference:
Mantooth, S. M., Abdou, Y., Saez-Ibañez, A. R., Upadhaya, S., & Zaharoff, D. A. (2024). Intratumoral delivery of immunotherapy to treat breast cancer: current development in clinical and preclinical studies. Frontiers in immunology, 15, 1385484. https://doi.org/10.3389/fimmu.2024.1385484
Other References:
Arnold, M., Morgan, E., Rumgay, H., Mafra, A., Singh, D., Laversanne, M., Vignat, J., Gralow, J. R., Cardoso, F., Siesling, S., & Soerjomataram, I. (2022). Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast (Edinburgh, Scotland), 66, 15–23. https://doi.org/10.1016/j.breast.2022.08.010
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet (London, England), 365(9472), 1687–1717. https://doi.org/10.1016/S0140-6736(05)66544-0
Riggio, A. I., Varley, K. E., & Welm, A. L. (2021). The lingering mysteries of metastatic recurrence in breast cancer. British journal of cancer, 124(1), 13–26. https://doi.org/10.1038/s41416-020-01161-4
