Dramatic Tumor Regression Was Displayed in New Approach to CAR T Therapy

Researchers from the Mass General Cancer Center, in collaboration with Mass General neurosurgeons, announced results from the first 3 patient cases included in a study assessing a new approach to chimeric antigen receptor (CAR) T-cell therapy for glioblastoma (GBM). Published in The New England Journal of Medicine, the results displayed a dramatic reduction in the individuals’ tumor size within days of a single treatment.

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CAR T-cell therapy uses a patient’s own cells to attack the cancer, which is the most personalized treatment for cancer, according to study authors. The therapy works by extracting the individuals’ cells, which are then modified to construct proteins on their surface, known as chimeric antigen receptors. These are then infected directly into the tumor. CAR T-cell therapies were previously approved to treat blood cancers, however, the use on tumors is restricted, according to the study authors.

“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 Bryan Choi, MD, PhD, neurosurgeon and associate director of the Center for Brain Tumor Immunology and Immunotherapy, Cellular Immunotherapy Program, Mass General Cancer Center and Department of Neurosurgery, in a press release. “Our approach combines 2 forms of therapy, allowing us to treat glioblastoma in a broader, potentially more effective way.”

The current treatment option was developed after years of research and partnership from the lab of Marcela Maus, MD, PHD, director of the Cellular Immunotherapy Program at the Mass General Cancer Center, Paula O’Keeffe chair in Oncology, and faculty of the Krantz Family Center for Cancer Research. “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,” said Maus in a press release.

In the past, the research team used the developed CAR T-cells to provide T-cell engaging antibody molecules (TEAMs) against a wild-type of epidermal growth factor receptor (EGFR). The study authors noted that EGRF is found in 80% of GBM cases.

The non-randomized, open label, single site phase 1 INCIPIENT trial (NCT05660369) aimed to evaluate the safety of CARv3-TEAM-E T cells in individuals with recurrent GBM. The study included 3 individuals, a 74-year-old man, a 72-year-old man, and a 57-year-old woman that were enrolled from March to July of 2023. However, before treatment the individuals were previously treated with standard-of-care radiation and temozolomide chemotherapy but faced a recurrence of cancer. The individuals T cells were then collected and infused back into the tumor.

Following a single infusion of the new CAR-TEAM cells, the 74-year-old man’s tumor displayed a regression quickly, with a EGRFvIII and EGRF decrease of blood and cerebrospinal fluid. Another patient displayed a 18.5% decrease in tumor size 2 days after treatment. Positive results remained in a 69-day follow-up with 60.7% tumor decrease, which was sustained over a 6-month period. Lastly, the woman displayed near-complete tumor regression only 5 days after a single infusion, according to study authors.

“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,” said Maus in a press release.

The promising results were short lived, as the study authors noted observed tumor progression was reported in all 3 cases—no progression greater than 6 months was the longest reported.

Despite displays of well tolerability of the infusions among all 3 individuals, the study authors noted that fevers and altered mental status was reported but expected.

“We report a dramatic and rapid response in these 3 patients. Our work to date shows signs that we are making progress, but there is more to do,” said co-author Elizabeth Gerstner, MD, a neuro-oncologist in the Department of Neurology at Massachusetts General Hospital, in a press release.

Reference

Preliminary Clinical Trial Results Show ‘Dramatic and Rapid’ Regression of Glioblastoma after Next Generation CAR-T Therapy. Mass General Brigham. News release. March 13, 2024. Accessed March 28, 2024. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/car-t-therapy-clinical-trial-for-glioblastoma-patients.