This study auditing the radiological volume parameters obtained from basic MRI sequences, specifically, the ratio of the initial T2 volume abnormality to the T1gad volume, provides information on treatment prognosis and pattern of relapse in glioblastoma.

There is currently a high unmet need for effective treatments for glioblastoma. While there are some therapies available, such as surgery, chemotherapy and radiation, they do not appear to be very effective in prolonging survival. In recent years, there has been a growing interest in immunotherapy and precision medicine, with researchers working to develop treatments that can more effectively target the specific genetic mutations and molecular pathways involved in glioblastoma growth. However, success in these efforts has been limited.

The researchers checked a glioblastoma database called The Cancer Genome Atlas to see if they could find any links between CHCHD2 and cancer. They discovered that, out of 577 samples, the CHCHD2 genes were more active in tumor cells than in normal tissue, and their activity was even higher in advanced glioblastoma cases.

In a first-in-human phase 1 trial in 41 patients with recurrent glioblastoma, an oncolytic virus treatment designed by Brigham researchers extended survival, especially among those with pre-existing viral antibodies. Therapy turns ‘immune desert’ into inflammatory cancer-fighting zone. Study demonstrated the safety and preliminary efficacy of a novel gene therapy for glioblastoma

Investigators from Brigham and Women’s Hospital reported the results of a Phase I clinical trial evaluating a novel engineered oncolytic herpes virus (oHSV) in patients with high-grade recurrent glioblastoma (rGBM). The candidate, designated CAN-3110 can infect cancer cells and stimulate an anti-tumor immune response. Findings from the first in human study, involving 41 patients, demonstrated the safety and preliminary efficacy of the novel gene therapy. The results also showed that treatment resulted in prolonged survival among a subgroup of recurrent GBM patients who were immunologically “familiar” with the virus and had pre-exiting viral antibodies.

The cancer-attacking virus is an oncolytic herpes simplex virus (oHSV), which is the same type of virus used in a therapy approved for the treatment of metastatic melanoma. Unlike other clinical oHSVs, this therapy includes the ICP34.5 gene, which is often excluded from clinical oHSVs because it causes human disease in unmodified forms of the virus. However, the researchers hypothesized that this gene may be necessary to trigger a robust, pro-inflammatory response necessary for attacking the tumor. Therefore, they designed a version of the oHSV1 that contains the ICP34.5 gene but is also genetically “programmed” not to attack healthy brain cells.

“There are two primary challenges in using mRNA therapies for cancer treatment. First, how do you accurately target the tumor cells in the body? Second, how do you produce enough of the therapy for human use?” Jiang said. “Our approach solves those two problems.” The quantity problem is solved by using a high-throughput system to produce mRNA-loaded extracellular vesicles from engineered cells. Host cells and a designer plasmid encoding the mRNA are subjected to two extremely short electric pulses, causing membranes inside the cell, as well as the cell membrane itself, to become temporarily permeable. This leads the cells to secrete many extracellular vesicles loaded with mRNA material that can then be collected.

A first-in-human trial indicates that treatment with an oncolytic virus is associated with increased survival in people with glioblastoma. In the phase I trial, 41 people with recurrent glioblastoma received intra-tumoural injection of an oncolytic herpes simplex virus (HSV) known as CAN-3110. The treatment produced an inflammatory tumour microenvironment that was favourable for immune responses against the tumour and was associated with increased survival time, particularly among people with HSV1 seropositivity.

When it comes to radiation therapy for glioblastoma, the brain is somewhat of a black box. Physicians typically treat this common and deadly form of brain cancer with radiation beams guided by CT imaging, a technique that helps them position the targeted radiation but doesn’t yield information about what’s inside the patient’s skull. In a practical sense, this means that clinicians don’t know whether a patient’s cancer has responded to ongoing treatment or progressed until additional images can be gathered, sometimes several months after treatment. For a fast-moving cancer like glioblastoma, that delay can be dangerous.

They found that after anti-CTLA-4 treatment, CD4+ T cells secreted a protein called interferon gamma that caused the tumor to throw up "stress flags" while simultaneously alerting microglia to start eating up those stressed tumor cells. As they gobbled up the tumor cells, the microglia would present scraps of tumor on their surface to keep the CD4+ T cells attentive and producing more interferon gamma-;creating a cycle that repeats until the tumor is destroyed.

Immunosuppression is a hallmark of the tumor microenvironment. TAMCs are a key driver of immunosuppression and therapy resistance. Because TAMCs compose 30 to 50 percent of the brain tumor mass, there’s an urgent need to develop new therapeutic strategies to target and modulate those immunosuppressive cells in brain tumors.

Scientists at St. Jude validated a cellular immunotherapy target called 78-kDa glucose-regulated protein (GRP78) in proof-of-principle experiments. The group also discovered a resistance mechanism whereby some tumors trick the cancer-killing immune cells into expressing GRP78, thereby turning off the immune cells or causing them to be killed, too. The research, which has implications for developing immunotherapy for the broad range of difficult-to-treat brain and solid tumors expressing GRP78, was published today in Cell Reports Medicine.

In a development fit for a Marvel movie, researchers from the U.K.'s University of Nottingham claim to have developed what they describe as the first “quantum therapeutic”—electrically-charged gold nanoparticles that trigger glioblastoma cells to kill themselves while leaving healthy cells intact. The scientists have filed a patent for the tech and believe it could eventually be sprayed on the brain during surgery.

The csGRP78 targeted CAR-T cells efficiently kill GBM tumor cells and GSCs both in vitro and in vivo, and ultimately suppress the xenograft tumors growth without obvious tissue injuries. Therefore, our study demonstrates that csGRP78 represents a valuable target and the csGRP78-targeted CAR-T cells strategy is an effective immunotherapy against GBM.

Researchers integrate scRNA-seq, spatial transcriptomics, and histology imaging data to show that spatial cellular architecture predicts glioblastoma prognosis.

Scientists have created a new zebrafish xenograft platform to screen for novel treatments for an aggressive brain tumor called glioblastoma, according to a new study by the Gerhardt and De Smet labs published in EMBO Molecular Medicine.

Overall, our results demonstrate that the reactive species generated by CAP regulate the cytotoxic potential of PAW and that the RONS concentrations depend on the plasma process parameters. The results reveal that combined treatments between PAW+TPT are able to reduce the metabolic activity and cell mass, as well as increase apoptotic cell death in glioblastoma cells.

They performed single-cell ribonucleic acid sequencing (scRNA-seq) of seven sets of patient-derived GBM stem cell cultures (GSCCs) combined with GBM-associated macrophage (GAM)-GBM co-cultures. Importantly, these GSCCs covered a broad spectrum of genetic aberrations frequently present in GBM.

By incorporating varying concentrations of collagenase to create an inhomogeneous collagen matrix, the study successfully demonstrated the strong dependency of tumor behavior on the stiffness of the surrounding extracellular matrix. The results showed that tumoroids exhibited higher growth rates and invasion lengths in response to higher concentrations of collagenase. These findings highlight the potential of investigating the impact of various matrix characteristics on tumor growth and invasion. Furthermore, the study employed a hybrid modeling technique that combined a continuum reaction–diffusion model and a discrete model to accurately capture the growth and invasion in an inhomogeneous environment.

Identification of pseudoprogression (PsP), defined as changes concerning for tumor progression that are, in fact, transient and related to treatment response, is critical for successful patient management. These temporary changes can produce new clinical symptoms due to mass effect and edema. Differentiating this entity from true tumor progression is a major decision point in the patient’s management and prognosis.