Skip links
groundbreaking-gene-therapy-receives-funding-for-treatment-of-aggressive-brain-cancer

Groundbreaking Gene Therapy Receives Funding for Treatment of Aggressive Brain Cancer

blank

The California Institute for Regenerative Medicine has awarded a groundbreaking $6 million grant to investigators at the University of Southern California (USC) who are at the forefront of developing an innovative genetic therapy aimed at combating glioblastoma, one of the most aggressive forms of brain cancer. This pioneering treatment, if successful, stands to be the first gene therapy specifically designed to leverage a novel, highly precise delivery system, minimizing collateral damage to healthy brain cells—an issue that has plagued traditional approaches to glioblastoma therapy.

Glioblastoma remains a formidable adversary in the realm of oncology, characterized by its rapid proliferation and pervasive mutability. This relentless cancer primarily afflicts adults and presents a daunting five-year survival rate of a mere 5 percent. The crux of the challenge lies in the tumor’s location within the delicate architecture of the brain, where its heterogeneous nature complicates effective treatment. Variations in tumor composition among different patients and even within the tumor’s own structure render conventional treatment protocols often inadequate.

David Tran, MD, PhD, who serves as the principal investigator on this initiative and a distinguished associate professor of neurological surgery at the Keck School of Medicine of USC, emphasizes the inherent difficulties faced by oncologists in attempting to tailor therapies for glioblastoma patients. “The personalized treatment you hear about for this type of cancer often feels like a game of whack-a-mole,” remarked Tran. This metaphor aptly underscores the perennial struggle to stay ahead of rapidly evolving tumor mutations that consistently evade therapeutic interventions.

The three-year grant awarded to the USC team, in collaboration with the Zolotukhin Lab at the University of Florida, seeks to bolster advancements in glioblastoma treatment methodology and push the research closer to clinical trials. At the heart of this initiative are three primary innovations, including the identification of new drug targets and the development of a refined delivery method for therapeutic agents.

Tran’s research team has made significant strides in employing artificial intelligence to sift through immense genetic databases. This groundbreaking approach has allowed researchers to pinpoint “master regulators”—crucial genes that not only define glioblastomas but are also vital for tumor survival. The identification of nine such master genes has revealed that seven of them are developmental genes, which are typically dormant after early fetal growth. It appears these malignant cells re-activate these genes to support their unchecked proliferation.

The seemingly insidious nature of tumor cells is evident in Tran’s findings, wherein tests aimed at depleting these developmental genes resulted in effective tumor collapse. Tran notes, “You only need to deplete a few of these master genes. Once they’re gone, the cancer doesn’t stand a chance,” highlighting a potential path forward in tackling the disease’s resistance to traditional therapies.

Simultaneously, the USC researchers have made strides in enhancing the delivery system for their therapies. Conventional viral vectors, such as adeno-associated viruses (AAV), have often proven to be indiscriminate, wreaking havoc not only on cancer cells but also on surrounding healthy tissue. Tran likens these outdated viral strategies to a “carpet-bombing” approach that lacks the necessary precision to combat brain cancers effectively.

In response, the USC team has meticulously engineered a library comprising approximately 10 billion variants of AAV viruses, eschewing the blanket-effect of previous methods in favor of a selective targeting technique. After rigorous screening, the researchers identified a promising variant, referred to as T6, which shows a marked preference for infecting glioblastoma cells while sparing normal brain tissue. Remarkably, initial tests in human-glioblastoma-bearing mouse models demonstrated a staggering cure rate approaching 70 to 90 percent, positioning the T6 virus as a potential game changer in gene therapy.

Creating a protocol for the clinical application of gene therapy requires addressing the logistical challenges of drug delivery, particularly in the context of difficult-to-access tumors. The traditional method known as convection-enhanced delivery (CED) has been fraught with limitations, often resulting in suboptimal therapeutic distribution. Tran points out the inherent blindness of the conventional CED technique, which typically relies on initial imaging to guide catheter placement into the tumor. This method frequently fails, especially when the catheter ends up in a blind pocket within the tumor’s architecture.

To enhance delivery efficiency, the USC research team, along with their collaborators, is developing advanced computational techniques aimed at elucidating the fluid dynamics within glioblastoma tumors. By mapping these flow patterns, the team aspires to equip surgeons with a greater understanding of how to optimize catheter positioning, ultimately leading to more effective drug diffusion throughout the tumor matrix.

As the research progresses, the USC team, comprised of neuropathologists, computational biologists, and neurosurgeons, will partner with the USC/CHLA cGMP facility. This facility provides the rigorous manufacturing standards required to ensure that all therapeutic interventions meet both safety and efficacy criteria outlined by the FDA. To that end, the team aims to conduct further preclinical testing to solidify and validate the encouraging results observed in laboratory conditions.

This moment is one of palpable optimism for Tran and his colleagues. Looking back to the early years of his career, he recalls a time when discussions with glioblastoma patients predominantly focused on preparing them for unfortunate outcomes. “Today, we’re talking about prolonging survival,” he remarked. Tran envisions a transformative future for patients diagnosed with glioblastoma, suggesting that the next five to ten years could lead to significant advancements in therapy and ultimately redefine the implications of such a diagnosis.

Through this innovative research initiative, the USC team is not just targeting a cancer; they are on the cusp of revolutionizing the landscape of glioblastoma treatment. With a promising combination of novel gene targeting techniques and advanced delivery systems, researchers hope to forge pathways toward a new dawn in the fight against one of humanity’s most challenging adversaries.

Subject of Research: Gene therapy for glioblastoma
Article Title: USC’s Innovative Gene Therapy for Glioblastoma Receives $6 Million Grant
News Publication Date: October 2023
Web References: USC Keck School of Medicine, Zolotukhin Lab at the University of Florida
References: Current peer-reviewed articles on glioblastoma treatment, gene therapy advancements, and AAV delivery systems.
Image Credits: USC Keck School of Medicine Archives

Keywords: Glioblastoma, Gene therapy, Targeted drug delivery, Tumor biology, Adeno-associated virus, Cancer research, Computational biology, Drug delivery systems, Immuno-oncology, Oncology innovations, Personalized medicine.

Tags: advanced neurological surgery techniquesCalifornia Institute for Regenerative Medicinechallenges of treating aggressive brain cancerfunding for brain cancer researchgene therapy for glioblastomaglioblastoma survival ratesimpact of funding on cancer researchinnovative cancer treatmentsnovel approaches to oncologyovercoming tumor heterogeneityprecision delivery systems in medicineUSC cancer research initiatives

Leave a comment

Explore
Drag