A collaborative effort aimed at bringing the promise of mobile treatment to patients with a fatal form of brain cancer has produced dramatic effects among the first patients to receive this new treatment. In an article published in The New England Journal of Medicine, researchers at the Mass General Cancer Center, a component of Mass General Brigham Health System, shared the effects of the first 3 patient instances in a phase 1 clinical trial comparing a new approach: CAR-T treatment for glioblastoma (GBM). The trial, known as INCIPIENT, is designed to compare the protection of CARv3-TEAM-E mobiles in patients with recurrent GBM. Just a few days after a single treatment, patients saw dramatic relief in their tumors, and one patient achieved near-total tumor regression. Over time, the researchers looked at tumor progression in those patients; However, given the promising initial effects of the strategy, the team will look for methods to prolong the durability of the response.
This is the story of bedside treatment, with a new mobile treatment designed in the laboratories of Massachusetts General Hospital and designed for patients to receive within five years, to address a pressing need. The CAR-T platform has revolutionized the way we think about treating cancer patients, but fake tumors like glioblastoma are still difficult to treat because not all cancerous tumors are exactly the same and tumors vary. Our technique combines two treatment bureaucracies, allowing us to treat glioblastoma in a more comprehensive and potentially more effective way. form. “
The new technique is the result of years of collaboration and innovation by the laboratory of Marcela Maus, MD, PhD, director of the Cellular Immunotherapy Program at Mass General Cancer Center, the Paula O’Keefe Chair of Oncology, and the Krantz School. Maus’ lab has assembled a team of participating scientists and trained staff to bring the lab’s next-generation genetically modified T cells to clinical trials in cancer patients.
“We have invested in the progression of the team to enable the translation of our immunotherapy inventions from our lab to the clinic, to the care of cancer patients,” Maus said. “These effects are exciting, but they’re also just the beginning: They tell us we’re on the right track to finding a treatment that has the potential to replace the prospects of this incurable disease. We haven’t cured the patients yet, but that’s our ambitious goal. “
Studies like this show the promise of a mobile treatment to treat incurable diseases. The Mass General Brigham Institute for Gene and Cell Therapy, where Maus is associate director and chief of mobile remedies, is helping translate clinical discoveries made by researchers into treatments for the first time in humans. clinical trials and, ultimately, life-changing remedies for patients. The Institute’s multidisciplinary technique sets it apart from others in the field, helping researchers promote new remedies and overcome the technological and clinical barriers of this new frontier.
CAR-T treatment works through the patient’s own cells to fight cancer; It is known as the most personalized way to treat cancer. A patient’s cells are removed, modified to produce proteins called chimeric antigen receptors on their surface, and then injected back into the frame to directly attack the tumor. The cells used in this study were fabricated through the Connell and O’Reilly Family Cell Manipulation Center at Dana-Farber/Harvard Cancer Center.
CAR-T treatments have been approved for the treatment of blood cancers, but their use for false tumors is limited. Solid tumors involve combined populations of cells, allowing some cancer cells to continue to evade detection through the immune system, even after CAR-T. Maus’ team is attempting to overcome this challenge of tumor heterogeneity through a state-of-the-art strategy that combines two hitherto separate strategies: CAR-T and bispecific antibodies, known as T-cell-attacking antibody molecules (TEAMs). The CAR-TEAM Glioblastoma Edition is designed to be injected directly into the patient’s brain.
In the past, Maus and his colleagues developed CAR-T cells to target a common cancerous mutation known as EGFRvIII, but when that alone had limited effects, his team engineered those CAR-T cells to deliver TEAM as opposed to wild-type EGFR. which is not detected under general conditions. Brain tissue is still expressed in more than 80% of GBM cases.
The mixture has shown promise in preclinical models of glioblastoma, encouraging the study team to look for clinical applications. In collaboration with Mass General’s neurosurgeons and neuro-oncologists, Elizabeth Gerstner, MD, and William Curry, MD, as well as mobile specialists in the delivery of treatments, were added. , Matthew Frigault, MD, and immunotreatment follow-up specialists, Kathleen Gallagher, PhD, the team presented INCIPIENT (Issue ClinicalTrials. gov, NCT05660369), a single-site, non-randomized, open-label, Phase 1 study.
Three patients were enrolled in the study between March 2023 and July 2023. The patients’ T cells were collected and remodeled into the new CAR-TEAM cell edit, which were then re-injected into each patient. examining.
All patients had been treated with radiation therapy and chemotherapy with temozolomide and were included in the trial after disease recurrence:
A 74-year-old man saw his tumor recede rapidly, but transiently, after a single infusion of new CAR-TEAM cells. The patient’s blood and cerebrospinal fluid showed a reduction in the number of copies of EGFRvIII and EGFR, becoming undetectable.
A 72-year-old man treated with a single infusion of CAR-TEAM cells. Two days after receiving CAR-TEAM cells, an MRI showed an 18. 5 percent reduction in tumor length. By day 69, the tumor had shrunk by 60. 7 percent. and the reaction was sustained for more than 6 months.
A 57-year-old woman treated with CAR-TEAM cells. An MRI five days after a single infusion of CAR-TEAM cells showed almost complete tumor regression.
Patients tolerated the infusions well, almost all had fever and altered intellectual prestige some time after the infusion, as would be expected from active treatment with CAR-T administered into the fluid surrounding the brain. All patients were observed in the hospital prior to discharge.
The authors note that despite the remarkable responses among the first 3 patients, they observed an eventual progression of the tumor in all cases; In one case there was no progression for more than six months. The progression was partly consistent with the CAR’s limited patience. -TEAM cells in the weeks after the infusion. As a next step, the team is contemplating serial infusions or preconditioning with chemotherapy to prolong the response.
“We are reporting a dramatic reaction in those 3 patients. Our work to date shows signs that we are making progress, but there is still much work to be done,” said co-author Elizabeth Gerstner, MD, a neuro-oncologist in the Department of Neurology at Massachusetts General Hospital.
General Brigham’s Mass
Choi, BD et al. (2024) CARv3-TEAM-E intraventricular T cells in recurrent glioblastoma. The New England Journal of Medicine is what je. org/10. 1056/NEJMoa2314390.
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