Glioblastoma

This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

The future of cancer treatment is being rewritten by CAR T cell therapy, the epitome of precision medicine. This therapy offers hope where traditional treatments fail by targeting cancer cells with unparalleled accuracy by utilizing the patient's own immune system. You should know more about the CAR T Cell therapy clinical trials if you want the best experience. The CAR T cell therapy clinical trials have many long-term advantages that you should be aware of.

At a joint event held by the Friends of Cancer Research and Parker Institute for Cancer Immunotherapy on Monday, cell therapy pioneer Carl June of the University of Pennsylvania Perelman School of Medicine revealed findings from a recent unpublished study from his group that looked at 783 patients who had received CAR-T treatments for HIV-1 or various cancers. Over more than 2,200 patient-years of observation, the group found 18 patients, or 2.3%, who developed secondary malignancies.

The promising findings, reported in Science Advances, involve CAR-T cell therapy, which supercharges the immune system to identify and attack cancer cells. The paper is titled "TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors."

"In less than 48 hours, we could see these tumors shifting from what we refer to as 'cold' -- immune cold, very few immune cells, very silenced immune response -- to 'hot,' very active immune response. That was very surprising given how quick this happened, and what that told us is we were able to activate the early part of the immune system very rapidly against these cancers, and that's critical to unlock the later effects of the immune response".

HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.

AZD1390, an ataxia telangiectasia mutant (ATM) kinase inhibitor, demonstrated a manageable safety profile in both recurrent and newly diagnosed glioblastoma (GBM) patients when given in combination with standard-of-care radiotherapy and showed preliminary efficacy in recurrent GBM patients, according to results from a global phase I trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2024, held April 5–10.

Glioblastoma (GBM), a highly immunosuppressive and often fatal primary brain tumor, lacks effective treatment options. GBMs contain a subpopulation of GBM stem-like cells (GSCs) that play a central role in tumor initiation, progression, and treatment resistance. Oncolytic viruses, especially oncolytic herpes simplex virus (oHSV), replicate selectively in cancer cells and trigger antitumor immunity—a phenomenon termed the “in situ vaccine” effect.

CAR T cells are a highly promising therapy for GBM with many potential target TAs identified. [...] However, there is still a long way ahead for CAR T cell therapy before it becomes a standard of care for the treatment of patients with GBM. Most clinical trials have proven that CAR T cells as a monotherapy are not particularly effective in solid tumors due to numerous immune escape mechanisms utilized by cancer cells (Lim and June, 2017). So far this appears to also be true for GBM, which additionally presents its own unique challenges to overcome. Among them, optimization of CAR T cell delivery into the brain is an important obstacle to overcome.

Researchers initiated a pioneering clinical trial using an advanced form of CAR-T therapy, enhanced by synthetic notch (synNotch) technology, to treat glioblastoma. This trial represents a significant shift towards targeted, safer cancer therapies. The synNotch technology allows CAR-T cells to precisely target tumor cells while sparing healthy tissue, potentially overcoming previous limitations of CAR-T in treating solid tumors like brain cancer. With this new approach, researchers aim to extend survival and improve the quality of life for patients with this aggressive cancer, marking a critical step in translational medicine from laboratory research to clinical application.

GBM constitutes an aggressive tumor associated with a dismal prognosis. Consequently, a compelling imperative exists for exploring innovative therapeutic interventions. CAR-T-cell therapy has garnered substantial attention within the realm of immunotherapy, showcasing promise across various tumor types, including GBM. Over time, refinements in the structures and functionalities of CAR-T cells have been pursued to enhance their efficacy in targeting tumor antigens. Nevertheless, the formidable challenges posed by the immunosuppressive TME, inter- and intra-tumoral heterogeneity, the immune-privileged status of the brain, and the hypoxic conditions prevailing in the tumor environment present formidable hurdles in the development of efficacious CAR-T-cell therapies for GBM.

En concreto, la terapia CAR-T, que ha prolongado la supervivencia de miles de pacientes con leucemia y otros cánceres sanguíneos, se está adaptando en la UC San Francisco para tratar a personas con glioblastoma, el tumor cerebral adulto más frecuente y mortal. Esta nueva versión más potente de CAR-T emplea una novedosa tecnología desarrollada en la UCSF denominada muesca sintética ('synNotch'), que protege el tejido sano del daño y permite que el tratamiento sea más eficaz.

Researchers demonstrated significant initial success using CAR-T therapy for glioblastoma, a notoriously deadly brain cancer. They detailed the outcomes of the first three patients in a Phase 1 clinical trial who experienced dramatic tumor reductions shortly after treatment. This innovative approach combines CAR-T cells with bispecific antibodies to more effectively target the heterogeneous cell populations within solid tumors. While the initial results show promise, the team is exploring ways to enhance the longevity of the therapy’s effectiveness.

Early data from patients eligible for evaluation at week 12 show two observations of stable disease, indicating no tumor progression, in VBI-1901 treatment arm (n=2/5; 40% disease control rate [DCR]) By comparison, no tumor responses have been observed in the control arm to-date (n=0/6; 0% DCR), with all patients seeing a 2-8x increase in tumor size by week 6. FDA has granted both Fast Track Designation and Orphan Drug Designation to VBI-1901 in recurrent GBM following encouraging Phase 1/2a study results

Treating glioblastoma is particularly difficult because the tumor recruits immunosuppressive macrophages—white blood cells that defend the body against disease and infections—into the tumor microenvironment to support the tumor's growth and make the tumor more resistant to therapy, said Peiwen Chen, Ph.D., assistant professor of Neurological Surgery and senior author of the study.

A new treatment to fight an extremely aggressive type of brain tumor showed promise in a pair of experiments with a handful of patients. The strategy is focused on treating glioblastoma, one of the deadliest types of cancer, which is only diagnosed at stage 4 and has a five-year survival rate of around 10%.

A flurry of new studies suggest scientists are finally figuring out how to harness the immune system to attack a ruthless form of brain cancer. While preliminary, the results offer hope that progress is possible against glioblastoma, the terrible form of cancer that so swiftly took the lives of Arizona Senator John McCain and President Joe Biden's son Beau.

For patients with recurrent glioblastoma, treatment with chimeric antigen receptor (CAR) T-cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, in addition to the wild-type EGFR protein, through secretion of a T-cell-engaging antibody molecule (TEAM; CARv3-TEAM-E) results in radiographic tumor regression, according to a study published online March 13 in the New England Journal of Medicine.

Researchers have embarked on a promising path by employing a dual-target CAR T-cell therapy against glioblastoma, the most aggressive form of brain cancer in adults. This innovative strategy focuses on attacking two specific proteins found in the tumors, marking a significant departure from traditional treatments. In a pioneering study, all six patients treated exhibited reduced tumor sizes, showcasing the potential of this approach to combat solid tumors effectively. However, the challenge remains to enhance the durability of these therapeutic effects, as tumor regrowth was observed in some patients.

In Mass General's test, tumors in three patients rapidly began shrinking within a couple of days, the researchers reported in the New England Journal of Medicine — "None of us could really believe it," Dr. Marcela Maus said

A Phase 1 clinical trial out of Massachusetts General Hospital in Boston recently used a new cell therapy in patients with recurring glioblastoma. Just days after a single treatment, the tumors dramatically reduced in size, according to the Mass General Cancer Center researchers. One patient even saw near-complete tumor regression.

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular pathogenesis and biology of this tumor in the past decade, the prognosis for GBM patients remains poor. GBM is characterized by aggressive biological behavior and high degrees of inter-tumor and intra-tumor heterogeneity. Increased understanding of the molecular and cellular heterogeneity of GBM may not only help more accurately define specific subgroups for precise diagnosis but also lay the groundwork for the successful implementation of targeted therapy.

According to medical literature, Ben Trotman should be grappling with a grim prognosis. Diagnosed with glioblastoma in October 2022, a type of brain cancer notorious for its rapid progression and dismal survival rates, Trotman's outlook was bleak. However, after participating in a world-first clinical trial, his cancer has effectively vanished, marking an unprecedented victory against one of the most aggressive cancers known to medicine.

There is no cure, but idroxioleic acid, or 2-OHOA, a novel drug derived from oleic acid — the key fatty acid in olive oil — will be tested on newly diagnosed glioblastoma patients in an upcoming study in London. The medication alters the walls of tumor cells to stop the cancer from growing or spreading.

Iovance Biotherapeutics’s Amtagvi is now the first FDA-approved treatment based on type of cell called a tumor-infiltrating lymphocyte. The regulatory nod in advanced melanoma also makes Amtagvi the first cell therapy approved for treating a solid tumor.