In a new study published in the New England Journal of Medicine, researchers from the Mass General Cancer Center have found promising results from a phase 1 clinical trial for a novel CAR-T therapy targeting glioblastoma (GBM), a deadly form of brain cancer.
The trial, named INCIPIENT, explored the safety and effectiveness of CARv3-TEAM-E T cells in treating patients with recurrent GBM.
Impressively, the first three patients treated showed dramatic reductions in tumor size, with one patient experiencing near-complete tumor regression shortly after receiving a single treatment.
Despite the initial success, the patients eventually showed signs of tumor progression. However, the encouraging early results have spurred the research team to investigate methods for enhancing the lasting effectiveness of the treatment.
This breakthrough represents a significant step forward from the lab to patient care, achieved within five years, aiming to address the urgent need for effective GBM treatments.
CAR-T therapy, a form of treatment that personalizes cancer care by modifying a patient’s cells to fight the cancer, has shown considerable success in treating blood cancers.
However, its application to solid tumors like GBM has been challenging due to the heterogeneity of cancer cells within the tumors.
The team at Mass General, led by Marcela Maus, MD, Ph.D., has developed a unique approach that combines CAR-T with bispecific antibodies, aiming to target the cancer more effectively.
This innovative strategy, directly injected into the patient’s brain, targets a common cancer mutation, EGFRvIII, and introduces T-cell engaging antibody molecules (TEAMs) against wild-type EGFR, commonly expressed in GBM but not in normal brain tissue.
The approach has shown promise in preclinical models, leading to the launch of the INCIPIENT trial.
The trial involved three patients between March and July 2023, whose T cells were collected, transformed into CAR-TEAM cells, and then infused back.
Despite experiencing expected side effects like fevers and altered mental status, the patients tolerated the treatment well, with significant tumor reductions observed.
However, the longevity of the CAR-TEAM cells and the subsequent tumor progression highlight areas for further research, including the possibility of serial infusions or chemotherapy preconditioning to extend the treatment’s effectiveness.
These initial results not only demonstrate a potent new option for GBM treatment but also open the door for future advancements in cell therapy for solid tumors.
The Mass General team’s commitment to transforming cancer care through innovative cell therapy research underscores the potential of such treatments to change the landscape of cancer treatment significantly.
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The research findings can be found in New England Journal of Medicine.
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