Genetic Engineering Publications - GEG Tech top picks

Glioblastoma is the most common fatal brain cancer, and patients still lack good treatment options. Patients typically receive chemotherapy, radiotherapy and surgery, but most relapse within a few months. However, CRISPR looks very promising as a therapeutic strategy for the aggressive and difficult-to-treat brain cancer known as primary glioblastoma, according to the results of a new study from the Gladstone Institutes. Using computational methods to analyze entire cancer cell genomes, the team dove deep into non-coding DNA to identify the repetitive code they all shared, even if they harbored a different variety of mutations. The researchers then programmed CRISPR to focus on repetitive DNA sequences present only in recurrent tumor cells to destroy these cells. Working with cell lines from a patient whose glioblastoma had recurred after previous treatments, the team used CRISPR to destroy tumor cells while sparing healthy cells.

Glioblastoma (GBM) is the most common and aggressive type of cancerous brain tumor in adults. People with GBM generally expect to live 12 to 18 months after diagnosis. Despite decades of research, there is no known cure for GBM, and treatments have only a limited effect on extending an individual's life expectancy. However, researchers have tested a technology that delivers CAR-T cells targeting two proteins commonly found in brain tumors: epidermal growth factor receptor (EGFR), estimated to be present in 60% of all GBMs, and interleukin-13 receptor alpha 2 (IL13Rα2), which is expressed in over 75% of GBMs. While CAR-T cell therapy for blood cancers is usually administered intravenously, the researchers administered these dual-targeted CAR-T cells intrathecally, by injection into the cerebrospinal fluid, so that the modified cells could reach the tumors more directly in the brain. Magnetic Resonance Imaging scans taken 24 to 48 hours after administration of dual-targeted CAR-T cells targeting EGFR and IL13Rα2 revealed a reduction in tumor size in all six patients, and these reductions were maintained up to several months later in a subgroup of patients. 

Chlorotoxin derived from scorpion venom has previously been shown to bind glioblastoma cells. Wang et al. designed a chimeric antigen receptor (CAR) based on chlorotoxin to surmount limitations of other glioblastoma-targeted CARs that have not been able to overcome tumor heterogeneity and antigen escape. They demonstrated that chlorotoxin binding captures a broader array of primary tumors than staining for previously identified antigenic targets. Chlorotoxin-directed CAR T cells were safe in mice and induced regression of orthotopic glioblastoma xenografts with no evidence of antigen escape. These toxin-based CAR T cells are distinct from conventional CAR design and could one day be used to deliver a poisonous blow to glioblastoma.