CAR-T (chimeric antigen receptor T-cell) therapy represents one of the most promising innovations in cancer treatment, leveraging a patient’s own immune cells to target malignancies. While its success in blood cancers is well-documented, researchers in 2024 are making strides to expand its utility to solid tumors such as glioblastoma, one of the most aggressive brain cancers.
Advancements in Glioblastoma Therapy
At Massachusetts General Hospital (MGH), a team led by Dr. Marcela Maus is pioneering an enhanced version of CAR-T cells, known as CAR-TEAM, specifically designed for glioblastoma. Traditional CAR-T therapies have struggled with solid tumors due to their heterogeneous nature and immunosuppressive environments. However, CAR-TEAM combines CAR-T cells with bispecific T-cell-engaging antibody molecules (TEAMs), enabling a broader attack on tumor cells.
A recent Phase 1 trial demonstrated encouraging results. Three glioblastoma patients treated with CAR-TEAM cells experienced rapid tumor regression, with MRI scans showing dramatic reductions within days. However, tumor progression was noted after several months, highlighting the need for sustained therapeutic strategies. The study’s approach, developed in collaboration with the Dana-Farber Cancer Institute, underscores the importance of translating laboratory innovations directly into clinical applications.
CAR-T for Other Solid Tumors
Beyond glioblastoma, researchers worldwide are exploring CAR-T therapies for various solid tumors. At the University of Pennsylvania, scientists are testing modified CAR-T cells to combat pancreatic and ovarian cancers. These advancements often rely on engineering T cells to overcome the physical barriers and immunosuppressive signals typical of solid tumors.
Notably, a team in China is testing the incorporation of cytokine delivery systems within CAR-T cells, enabling these modified cells to remain active within the harsh tumor microenvironment. Preliminary trials in 2024 have shown promise in extending survival rates for patients with advanced gastrointestinal cancers.
Challenges in Scaling CAR-T Therapies
Despite its potential, CAR-T therapy faces hurdles in cost, accessibility, and side effect management. Manufacturing CAR-T cells is a time-intensive and costly process, requiring personalised cell modification for each patient. Efforts are underway to develop “off-the-shelf” CAR-T therapies using donor cells, which could dramatically reduce costs and increase availability.
Side effects, such as cytokine release syndrome and neurotoxicity, remain significant concerns. Researchers at MGH and other institutions are investigating preconditioning regimens and checkpoint inhibitors to mitigate these risks and enhance the durability of responses.
The Future of CAR-T
As CAR-T therapy continues to evolve, 2024 marks a turning point in its application to solid tumors. The insights gained from early trials in glioblastoma and other cancers are paving the way for more refined, effective, and accessible treatments. Collaborative efforts between academic institutions and biotechnology companies remain essential in overcoming the scientific and logistical challenges that lie ahead.