An Old Foe Shows Some New Cracks in its Armor

Glioblastoma, one of the most aggressive and lethal brain cancers, may finally be showing a few cracks in its armor. In Boston, researchers at Massachusetts General Hospital unveiled early results from a Phase 1 trial in which a next-generation CAR-T cell therapy induced rapid, dramatic regression of recurrent glioblastoma tumors. Dubbed “CARv3-TEAM-E T cells,” the approach pairs genetically engineered T cells with bispecific antibody molecules (so-called “TEAMs”) to address tumor heterogeneity. In the first three patients, one achieved near-complete tumor regression within days after a single infusion; others showed substantial reductions (e.g. over 60%) that were sustained for several months. ⁽¹⁾

Meanwhile, at Mayo Clinic, a different strategy is showing promise for older patients with newly diagnosed glioblastoma: shortening and refining the radiation treatment course. The “SAGA” trial combines advanced imaging with hypofractionated proton beam therapy—delivered over one to two weeks rather than the traditional three to six. In this older population (65+), median overall survival rose to 13.1 months (versus the expected 6 to 9), and some patients with favorable tumor genetics exceeded even that, living for nearly two years after treatment. Importantly, side effects were manageable and quality of life held up, suggesting that treatment intensity and duration may be optimized in ways that reduce burden without sacrificing benefit. ⁽²⁾

In Australia, researchers employing the Brain Perioperative (BrainPOP) platform broke new ground in studying low-grade gliomas (LGGs), particularly those with mutated IDH1, a gene whose alteration defines a distinct and somewhat slower-progressing subgroup. The trial, unique in its design, treated patients before any radiation or chemotherapy with an IDH1 inhibitor and collected tumor samples both before and after treatment to observe how the drug works in human brain tumors. Following treatment, there were signs of immune activation and biochemical changes in the tumors, offering what investigators call “unprecedented insight” into how IDH1 mutant gliomas respond, and giving hope that this class of tumors, long considered incurable, may be susceptible to targeted molecular therapies. ⁽³⁾

Taken together, these advances illustrate a two-front approach on brain cancer: one through highly targeted immunotherapy for recurrent disease, the other through refined radiation and molecular-targeted therapy earlier in the disease course. Still, challenges remain: the CAR-T approach showed that while tumor shrinkage could be rapid and large, relapse eventually occurred in all patients studied so far.¹ The studies are early, with small numbers; and for many patients, genetic markers, or tumor types that respond favorably may be the exception rather than the rule. But for patients, families, and researchers long accustomed to incremental steps, these represent hopeful leaps—new strategies not only to extend survival, but meaningfully improve the quality of life, and point to Better Healthcare Tomorrow™.

Sources: 

1. https://www.massgeneral.org/news/press-release/clinical-trial-results-show-dramatic-regression-of-glioblastoma-after-next-generation-car-t-therapy 

2. https://newsnetwork.mayoclinic.org/discussion/breakthrough-in-treatment-approach-showing-promise-in-the-fight-against-glioblastoma-the-deadliest-and-most-aggressive-type-of-brain-cancer/ 

3. https://thebraincancercentre.org.au/world-first-clinical-trial-brings-new-hope-for-brain-cancer-patients/ 

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