Clinical Perspectives

Blocking Immune Checkpoints in Glioblastoma

December 28, 2015

Blocking Immune Checkpoints Photo Courtesy of Merck & Co., Inc..jpg Clinical trials investigating the safety and benefit of this promising group of drugs in patients with glioblastoma have launched

Solmaz Sahebjam, MD

Immune checkpoints are proteins in our cells that have been developed to avoid autoimmunity and destruction of normal cells by our immune system. They normally terminate immune responses after antigen activation.

However, some tumors hijack this pathway to evade the body’s immune response to the cancer. In a normal state, our immune system recognizes the tumor cells and mounts immune response to destroy the cells. In certain tumor types, cancer cells express PD-L1 and PD-L2. These proteins can interact with receptors on immune cells. By doing so, they inactivate the immune cells and suppress their attack on cancer cells.

Antibodies targeting PD-1 or its ligand PD-L1 are delivering impressive results in a wide range of advanced cancer types such as melanoma, lung cancer, renal cell carcinoma, and bladder cancer. Tumor shrinkage has been reported in up to 50% of patients who received these agents through clinical trials. Moreover, these drugs have resulted in unprecedented durable response in a large number of patients.

Currently, two of these antibodies have received regulatory approvals. On September 15, the Food and Drug Administration granted accelerated approval to anti-PD-1 antibody, pembrolizumab (Keytruda), for the treatment of patients with advanced melanoma. Earlier in July, nivolumab (Opdivo) was approved in Japan for use in advance melanoma.

Expression of PD-L1 has been shown in tumor samples from patients with glioblastoma, andPD-L1 is one of the dominant molecular participants in the suppression of glioblastoma immunity. Furthermore, blockage of PD-1/PD-L1 in animal models of glioblastoma has shown exciting results.

Clinical trials investigating the safety and benefit of this group of drugs in patients with glioblastoma have launched this year. At Moffitt Cancer Center, we are actively involved in research and development of clinical trials bringing these therapeutic agents to patients with glioblastoma with the goal of improving their lives.