Clinical Uses of Immunotherapy for Adults with Recurrent Glioblastoma

Meagana Olivet^*
*Correspondence: Meagana Olivet, Department of Oncology, University of Alabama at Birmingham, Birmingham, USA, Email:

Introduction

Glioblastoma (GBM) is the most aggressive form of primary brain tumor in adults, characterized by its high invasiveness and resistance to conventional therapies. Despite advances in surgical techniques, radiation therapy, and chemotherapy, the prognosis for patients with recurrent glioblastoma remains dismal. In recent years, immunotherapy has emerged as a promising approach to combat this devastating disease. This article explores the clinical uses of immunotherapy in the management of adult patients with recurrent glioblastoma, focusing on the various immunotherapeutic strategies, clinical trials, challenges, and future prospects. Glioblastoma (GBM) is a highly malignant brain tumor with a median survival of only 12-15 months after diagnosis, even with aggressive treatment. The standard of care involves maximal surgical resection followed by radiotherapy and temozolomide chemotherapy. Unfortunately, the vast majority of GBM patients will experience recurrence, highlighting the urgent need for effective treatment options [1].

Immunotherapy has shown remarkable potential in various malignancies, and its application in recurrent glioblastoma has garnered significant attention in recent years. This article will discuss the clinical uses of immunotherapy, highlighting the various approaches, their mechanisms of action, and their implications for patients with recurrent glioblastoma. Checkpoint inhibitors, such as pembrolizumab and nivolumab, target programmed cell death protein or its ligand. By blocking these immune checkpoints, the inhibitory signals on T cells are removed, allowing enhanced T cell-mediated immune responses against tumor cells. Clinical trials with checkpoint inhibitors have shown promising results in recurrent glioblastoma patients, with some achieving durable responses and prolonged survival. Tumor vaccines aim to stimulate the patient's immune system against specific antigens expressed on tumor cells. Several personalized vaccines have been developed for recurrent glioblastoma patients, utilizing tumor-specific neoantigens identified through genomic sequencing [2].

These vaccines have shown potential in inducing immune responses, but their efficacy may be limited by the immunosuppressive tumor microenvironment.CAR T-cell therapy involves modifying a patient's T cells to express a synthetic receptor that recognizes tumor-specific antigens. CAR T cells have demonstrated impressive results in hematologic malignancies, and ongoing clinical trials are investigating their potential in glioblastoma. However, challenges include identifying suitable target antigens and overcoming the immunosuppressive nature of the brain. Numerous clinical trials have evaluated the safety and efficacy of immunotherapeutic agents in recurrent glioblastoma. Some trials have reported encouraging results, while others have shown limited benefits. The heterogeneity of glioblastoma and the complexity of the immune system present challenges in the design and interpretation of these trials [3].

Description

CAR T-cell therapy is a novel approach in recurrent glioblastoma, and early-phase trials have shown feasibility and safety. However, the clinical outcomes have been modest, possibly due to the difficulty in identifying ideal target antigens and the challenges of CAR T-cell infiltration into the brain. The brain has a unique immune microenvironment that hinders immune cell infiltration and activation. Tumors can also exploit immune checkpoints to evade immune attacks. Overcoming these barriers is crucial for successful immunotherapy. Identifying patients who will respond to immunotherapy remains a challenge. Biomarkers predictive of treatment response need to be developed to guide patient selection. Combining immunotherapy with other treatment modalities, such as targeted therapies or radiation, may enhance therapeutic responses and improve patient outcomes. Rational combinations based on preclinical evidence and clinical trials are being explored [4].

Early-phase clinical trials with checkpoint inhibitors have demonstrated durable responses and increased overall survival in some recurrent glioblastoma patients. For instance, a phase I study involving pembrolizumab showed a 6-month progression-free survival rate of 25.5% in recurrent GBM patients. However, response rates have varied across different trials, and patient selection remains critical for identifying potential responders. Clinical trials evaluating personalized tumor vaccines have shown promise in stimulating immune responses. A phase II trial using an EGFRvIII-targeted vaccine in recurrent glioblastoma patients demonstrated improved overall survival and progression-free survival compared to historical controls. Nonetheless, the complexity of vaccine production and individual variability hinder widespread implementation [5].

Conclusion

The high cost of immunotherapy and its limited availability in some regions raise concerns about equitable access to these treatments. Immunotherapy holds promise as a novel treatment option for adults with recurrent glioblastoma. Checkpoint inhibitors, tumor vaccines, and CAR T-cell therapy have demonstrated encouraging results in early-phase clinical trials. However, challenges related to the immunosuppressive tumor microenvironment, patient selection, and treatment cost remain to be addressed. Ongoing research, clinical trials, and collaborations among researchers and clinicians are essential to unlock the full potential of immunotherapy in the fight against recurrent glioblastoma and improve the quality of life for these patients. Checkpoint inhibitors are a class of immunotherapeutic agents that target immune checkpoints, such as programmed cell death protein and its ligand PD-L1, to restore the immune system's ability to recognize and attack cancer cells. Pembrolizumab and nivolumab are two checkpoint inhibitors that have shown promise in recurrent GBM. However, their efficacy has been modest, indicating the need for combination therapies to improve outcomes.

Acknowledgement

None.

Conflict of Interest

There is no conflict of interest by author.

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