Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer that affects the lining of the lungs and is primarily caused by exposure to asbestos. The prognosis for patients with MPM is poor, with a median survival of 12-18 months. However, in recent years, there has been significant progress in the development of immunotherapeutic agents for MPM that may offer new treatment options for patients.
Immunotherapy is a type of cancer treatment that enhances the body’s immune system to fight cancer cells. While traditional chemotherapy and radiation therapy can damage healthy cells along with cancer cells, immunotherapy targets cancer cells specifically and leaves healthy cells unharmed. Here are some of the new immunotherapeutic agents being developed for MPM:
PD-1/PD-L1 inhibitors: Programmed death-1 (PD-1) is a protein receptor found on the surface of T-cells, which are a type of immune cell that can identify and attack cancer cells. However, cancer cells can express a protein called programmed death-ligand 1 (PD-L1), which binds to PD-1 and inhibits the T-cells from attacking the cancer cells. PD-1/PD-L1 inhibitors are a type of immunotherapy that block this interaction, allowing the T-cells to attack the cancer cells. Several PD-1/PD-L1 inhibitors are currently being investigated in clinical trials for MPM, including pembrolizumab, nivolumab, and durvalumab.
CTLA-4 inhibitors: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is another protein receptor found on the surface of T-cells. When activated, CTLA-4 inhibits the immune response against cancer cells, allowing the cancer to continue to grow. CTLA-4 inhibitors are a type of immunotherapy that block this inhibitory signal, allowing the immune system to attack the cancer cells. One CTLA-4 inhibitor, ipilimumab, is currently being investigated in clinical trials for MPM.
CAR-T cell therapy: Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that involves genetically modifying a patient’s T-cells to express a CAR, which is a receptor that targets a specific antigen found on cancer cells. The modified T-cells are then infused back into the patient, where they can identify and attack cancer cells that express the targeted antigen. CAR-T cell therapy has shown promising results in clinical trials for other types of cancer, and several CAR-T cell therapies are currently being developed for MPM.
TLR agonists: Toll-like receptors (TLRs) are proteins found on the surface of immune cells that can recognize and respond to specific molecules found on the surface of bacteria, viruses, and cancer cells. TLR agonists are a type of immunotherapy that activate TLRs, leading to the activation of immune cells and the production of cytokines, which can help to attack cancer cells. Several TLR agonists are currently being investigated in clinical trials for MPM, including SD-101 and IMO-2125.
Oncolytic viruses: Oncolytic viruses are viruses that can selectively infect and kill cancer cells while leaving healthy cells unharmed. Oncolytic viruses can also stimulate the immune system to attack cancer cells. Several oncolytic viruses are currently being investigated in clinical trials for MPM, including ONCOS-102 and HF10.
In conclusion, while the prognosis for patients with MPM remains poor, there is hope that new immunotherapeutic agents may offer new treatment options for patients. PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, CAR-T cell therapy, TLR agonists, and oncolytic viruses are some of the new immunotherapeutic agents being developed for MPM that may improve patient outcomes in the future. Clinical trials are ongoing to determine the safety and efficacy of these agents, and it is hoped that they will ultimately lead to improved survival rates for patients with MPM.
