Clinical trials for innovative glioblastoma treatment have yielded rapid success, with certain patients witnessing a significant decrease in tumor size shortly after initiating treatment.
Mass General Cancer Center researchers in Massachusetts have unveiled the findings from the initial phase of a clinical trial involving CAR-T cell therapy for glioblastoma, a lethal form of brain cancer.
CAR-T cell therapy, recipient of the Nobel Prize in Medicine, utilizes a patient’s own immune cells to combat cancer, making it the most personalized treatment option for the option for the disease at present.
The procedure involves extracting a patient’s cells, modifying them to express specific proteins on their surface, and reintroducing them into the body to directly target the tumor. Although CAR-T therapies have gained approval for blood cancers, their application in treating solid tumors remains restricted.
The INCIPIENT trial, focused on assessing the safety of CARv3-TEAM-E T cells in patients with recurrent glioblastoma, the most prevalent brain cancer in adults, was designed for this purpose. By merging CAR-T with bispecific antibodies, known as T-cell engaging antibody molecules or “TEAMs,” the approach exhibited promise in preclinical models of glioblastoma.
Published in the New England Journal of Medicine, the study enrolled three patients between March and July 2023. Patients’ T cells underwent transformation into the updated CAR-TEAM cells, which were subsequently infused back into each patient.
While the patients generally tolerated the infusions well, nearly all experienced fevers and altered mental status shortly after infusion. Within days of receiving a single treatment, patients observed significant reductions in tumor size, with one individual achieving near-complete regression in just five days following treatment.
“The CAR-T platform has revolutionized how we think about treating patients with cancer, but solid tumors like glioblastoma have remained challenging to treat because not all cancer cells are exactly alike and cells within the tumor vary,” said assistant professor Bryan Choi from Harvard Medical School.
“This is a story of bench-to-bedside therapy, with a novel cell therapy designed in the laboratories of Massachusetts General Hospital and translated for patient use within five years, to meet an urgent need.”
A 72-year old male patient experienced a sustained 60.7% reduction in his tumor size over a period of six months, whereas a 57-year-old female patient achieved nearly complete tumor regression within five days following a single infusion.
While the team finds their results promising, they emphasize the necessity for further research to refine this treatment approach.
Marcela Maus, director of the Cellular Immunotherapy Program at the Mass General Cancer Center, said, “We’ve made an investment in developing the team to enable translation of our innovations in immunotherapy from our lab to the clinic, to transform care for patients with cancer.”
“These results are exciting, but they are also just the beginning—they tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”
“We haven’t cured patients yet, but that is our audacious goal,” Maus added.
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