Immunotherapy of Multiple Myeloma: Exploring Molecular Mechanisms

Immunotherapy of Multiple Myeloma: Exploring Molecular Mechanisms Multiple myeloma, a malignancy of plasma cells, has traditionally been treated with chemotherapy, radiation, and stem cell transplantation. However, immunotherapy has revolutionized the treatment landscape, offering new hope for patients by leveraging the body's immune system to target cancer cells more effectively. The Role of Immune Checkpoints Immune checkpoints regulate immune activation and maintain self-tolerance. In multiple myeloma, cancer cells exploit these checkpoints to evade immune detection. Programmed death-۱ (PD-۱) and its ligand PD-L۱ are key players in this mechanism. Myeloma cells express PD-L۱, which binds to PD-۱ receptors on T-cells, inhibiting their activity. Checkpoint inhibitors like pembrolizumab and nivolumab block this interaction, reactivating T-cells to attack myeloma cells. Bispecific T-Cell Engagers (BiTEs) CAR T-cell therapy is a groundbreaking approach in multiple myeloma. This personalized treatment involves genetically engineering a patient’s T-cells to express Chimeric Antigen Receptors (CARs) that recognize antigens in myeloma cells. A primary target in this therapy is BCMA (B-cell maturation antigen), which is highly expressed in myeloma cells. CAR T-cell therapy targeting BCMA has shown significant efficacy in clinical trials, especially in patients with refractory myeloma, offering high response rates and potential long-term remission. Bispecific T-Cell Engagers (BiTEs) Bispecific T-cell engagers (BiTEs) represent another innovative approach. BiTEs are engineered proteins that bind simultaneously to T-cells and myeloma cells, bringing them into close proximity to facilitate cancer cell destruction. Blinatumomab is a BiTE that targets CD۳ on T-cells and BCMA on myeloma cells, enhancing the immune system’s ability to kill cancer cells. Monoclonal Antibodies Monoclonal antibodies (mAbs) are specifically designed to target myeloma cell antigens. Daratumumab, which targets the CD۳۸ protein on myeloma cells, and elotuzumab, which targets SLAMF۷, are two mAbs that have shown significant therapeutic effects. Daratumumab triggers immune responses that kill myeloma cells, while elotuzumab enhances natural killer (NK) cell activity to promote cancer cell destruction. Vaccines and Immune Modulators Cancer vaccines aim to stimulate the immune system to recognize and attack myeloma cells by using myeloma-specific antigens. Immune modulators like lenalidomide and pomalidomide boost the immune response by enhancing T-cell and NK cell activity while suppressing regulatory T-cells that dampen immune function. These modulators are often used in combination with other therapies to increase their effectiveness. Overcoming Resistance Resistance to immunotherapy is a challenge in multiple myeloma, with cancer cells adapting mechanisms to evade immune detection. Combination therapies targeting multiple pathways are being explored to overcome this resistance. A better understanding of the tumor microenvironment and its role in immune evasion is key to advancing immunotherapy. Conclusion Immunotherapy has transformed multiple myeloma treatments, offering durable responses and potential cures. Checkpoint inhibitors, CAR T-cells, BiTEs, and monoclonal antibodies have shown significant success, and ongoing research into overcoming resistance is crucial to further improving patient outcomes.

کلیدواژه ها:

Multiple Myeloma ، Immunotherapy ، Cancer ، Tumor microenvironment