Journal of Neuro-Oncology and Neuroscience Open Access

Emerging Therapies for Glioblastoma: From Immunotherapy to Gene Editing

Carmine Abate^* Department of Oncology, University of Melbourne, Australia
^*Correspondence: Carmine Abate, Department of Oncology, University of Melbourne, Australia, Email:

Received: 02-Dec-2024, Manuscript No. IPJNO-24-22236; Editor assigned: 04-Dec-2024, Pre QC No. IPJNO-24-22236 (PQ); Reviewed: 18-Dec-2024, QC No. IPJNO-24-22236; Revised: 23-Dec-2024, Manuscript No. IPJNO-24-22236 (R); Published: 30-Dec-2024, DOI: 10.21767/2572-0376.9.4.31

Introduction

Glioblastoma is the most aggressive primary brain tumor, characterized by rapid progression, extensive heterogeneity, and a grim prognosis despite the current standard of care—surgical resection, radiation, and chemotherapy with temozolomide. To address this challenge, researchers are exploring innovative therapeutic approaches, including immunotherapy, gene editing, and other cutting-edge modalities, aiming to overcome GBM’s resistance mechanisms and improve patient outcomes. Immunotherapy represents a revolutionary shift in GBM treatment, leveraging the immune system to target tumor cells. While it has demonstrated success in other cancers, GBM presents unique hurdles, such as the immunosuppressive tumor microenvironment and the Blood-Brain Barrier (BBB). Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-CTLA-4 antibodies) aim to reactivate T cells suppressed by the GBM’s TME. While early trials showed limited efficacy due to the “cold” immune microenvironment of GBM, combining checkpoint inhibitors with other modalities, such as radiation or vaccines, may enhance therapeutic outcomes. Vaccines such as DCVax-L, which use patient-derived dendritic cells loaded with tumor antigens, aim to generate a robust immune response against GBM cells. Results from clinical trials have demonstrated prolonged survival in some patients, signaling their potential as a complementary therapy.

Description

Chimeric Antigen Receptor T (CAR-T) cell therapy involves engineering T cells to target GBM-specific antigens, such as EGFRvIII or IL13Rα2. While CAR-T therapy has faced challenges like antigen heterogeneity and limited persistence in the brain, ongoing research focuses on optimizing CAR-T cells for better penetration and sustained activity. Oncolytic virotherapy uses genetically modified viruses that selectively infect and kill tumor cells while stimulating an anti-tumor immune response. Viruses such as Toca 511 and DNX-2401 are under investigation, with encouraging early-phase trial results suggesting potential synergy with other therapies. Gene editing technologies, particularly CRISPR-Cas9, have opened new avenues for GBM treatment by directly targeting the tumor’s genetic drivers. These techniques offer unprecedented precision in altering genes involved in tumor growth, resistance, and survival. CRISPR-Cas9 can be used to knock out oncogenes such as EGFR or restore tumor suppressor genes like PTEN and TP53. By correcting these mutations, researchers aim to disrupt the pathways driving tumor progression. Gene editing can sensitize GBM cells to chemotherapy or radiation by modulating resistance pathways, such as the MGMT gene, which confers resistance to temozolomide. Silencing MGMT expression using CRISPR could improve the efficacy of standard therapies. Advances in nanoparticle technology and viral vectors have improved the delivery of gene-editing tools across the BBB.

Conclusion

Emerging therapies for glioblastoma, from immunotherapy to gene editing, represent a paradigm shift in tackling this formidable cancer. While hurdles remain, the integration of these innovative approaches holds the potential to transform GBM treatment, offering new hope to patients and families affected by this devastating disease. As research progresses, a multimodal, personalized approach will likely define the future of GBM therapy, bridging the gap between cutting-edge science and clinical practice. Overcoming the BBB remains a major obstacle for the effective delivery of therapeutics, particularly gene-editing tools and immune cells. Ensuring specificity and minimizing off-target effects, especially with gene-editing technologies, are critical for clinical application. Advanced therapies like CAR-T cells and CRISPR are resource-intensive, limiting their availability to broader populations.