Breaking Through Glioblastoma, the ‘Unconquerable’ Brain Tumor, With New CAR-T Technology

New research aimed at conquering glioblastoma (Glioblastoma, GBM), known as the “king of brain tumors,” is raising expectations for new treatment strategies.

Chinese biotech publication BioOn reported on the 28th (local time) on major glioblastoma research findings published in leading international journals, including Cell, Nature and Science. In particular, multifaceted approaches centered on next-generation CAR-T (chimeric antigen receptor T-cell) therapies and characterization of the tumor microenvironment (TME) stood out.

CAR-T therapies are by far the most closely watched area. UCLA researchers developed “armored CAR-T” cells designed to secrete the immune-stimulating cytokines IL-12 and DR-18, and published findings in Cancer Research showing enhanced tumor control and reduced adverse effects. The same researchers also reported in Science Translational Medicine on CAR-T cells that locally block VEGF (vascular endothelial growth factor), which promotes tumor growth.

Efforts to identify new targets are also continuing. A McMaster University research team reported in Science Translational Medicine that a next-generation CAR-T candidate targeting uPAR (urokinase receptor) on the surface of cancer cells showed tumor-eradicating effects in preclinical studies. A University of Pennsylvania research team reported in Cell that activation of NK cells (natural killer cells) was associated with favorable outcomes in a treatment involving direct CAR-T infusion into the ventricles, identifying a potential clue for predicting treatment response.

Research aimed at understanding glioblastoma’s complex tumor microenvironment and fundamental biological characteristics is also active. University of Miami researchers reported in Nature Cancer that the neurotransmitter GABA induces a tumor-supportive immune response specifically in females, suggesting the possibility of sex-specific treatment.

In addition, a Massachusetts General Hospital research team succeeded in using an oncolytic virus that selectively destroys cancer cells to help immune cells penetrate deep into tumors (Cell), while a Georgetown University research team developed the artificial intelligence (AI) algorithm “scFOCAL,” opening a path toward predicting patient-specific drug combinations (Nature Communications).

These studies suggest that, given the recognition that glioblastoma can no longer be conquered with a single therapy, multifaceted strategies are needed, including advancing CAR-T technology, identifying new targets, controlling the tumor microenvironment and developing personalized treatments.