For Recurrent Glioblastoma, Immunotherapy Before Surgery Appears to Help More Than Afterward
Targeted News Service
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In recent years, immunotherapy drugs, which harness the body's immune system to destroy cancer cells, have been shown to be helpful in treating people with advanced or metastatic cancer. But the drugs have yet to show any benefit in helping people with glioblastoma, an aggressive and deadly form of brain cancer. On average, most people with recurrent glioblastoma live for just six to nine months.
The study, published online in Nature Medicine, was co-led by
In the study, people treated with the drug prior to surgery lived nearly twice as long after surgery as the average life expectancy for people with the disease.
Pembrolizumab is an antibody that works by blocking a checkpoint protein called PD-1, which stops T cells from attacking cancer cells. Cancer cells often use PD-1 to keep T cells at bay. But inhibiting the engagement of the protein with a checkpoint inhibitor drug like pembrolizumab enables the immune system to better attack the cancer.
"The results are very encouraging," said Prins, the study's senior author. "This is the first hint that immunotherapy can have a clinical benefit for patients with malignant brain tumors --and help prevent future recurrences."
The trial, which took place at seven medical centers throughout the
Those who received the drug before surgery survived an average of 417 days, those who received the drug after surgery lived an average of 228 days.
"By administering the immunotherapy before surgery, we activated the T cells within the tumor that were previously functionally impaired, which is essentially what helped extend people's lives," Cloughesy said.
In a person with cancer, if antigen-specific T cells are present and impaired by the tumor and the surrounding microenvironment, they can be awakened by the drug prior to surgery. In contrast, after surgery, the drug doesn't stimulate patients' T cells because those T cells are removed with the tumor.
The findings could be significant because there have been few major advances in the treatment of glioblastoma in the past two decades, and because it could be a step toward developing new biomarkers for the disease.
"This data may lead us to a better understanding of the mechanisms by which some patients generate significant immune responses to this therapy while others do not," said Prins, who is also a research member of the
The team is now testing the immunotherapy in combination with vaccines and other checkpoint inhibitors.
"This isn't a very big study, and our data need to be replicated, but we have a foot in the door," Cloughesy said. "We have found a way to use these checkpoint inhibitors in glioblastoma that we previously thought were ineffective. We now have a rational and logical way to develop immunotherapies going forward and a clinical development process for doing it."
The pilot study was also conducted at the
The study's co-senior author is
The study was funded in part by the