Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives

Abstract

Despite decades of research and the best up-to-date treatments, grade 4 Glioblastoma (GBM) remains uniformly fatal with a patient median overall survival of less than 2 years. Recent advances in immunotherapy have reignited interest in utilizing immunological approaches to fight cancer. However, current immunotherapies have so far not met the anticipated expectations, achieving modest results in their journey from bench to bedside for the treatment of GBM. Understanding the intrinsic features of GBM is of crucial importance for the development of effective antitumoral strategies to improve patient life expectancy and conditions. In this review, we provide a comprehensive overview of the distinctive characteristics of GBM that significantly influence current conventional therapies and immune-based approaches. Moreover, we present an overview of the immunotherapeutic strategies currently undergoing clinical evaluation for GBM treatment, with a specific emphasis on those advancing to phase 3 clinical studies. These encompass immune checkpoint inhibitors, adoptive T cell therapies, vaccination strategies (i.e., RNA-, DNA-, and peptide-based vaccines), and virus-based approaches. Finally, we explore novel innovative strategies and future prospects in the field of immunotherapy for GBM.

Revolutionizing Brain Tumor Care: Emerging Technologies and Strategies

“…TMZ is typically taken seven days a week for six weeks at a dosage of 75 mg/m 2 during the initial treatment phase. After this, patients undergo six cycles of adjuvant TMZ therapy at a dosage ranging from 150 to 200 mg/m 2 [ 8 ]. Each cycle spans 28 days and includes five days of TMZ administration.…”

“…Additionally, GBMs are heterogeneous, with a lower mutational burden and reduced PD-L1 expression compared to other responsive tumor types. Although ICI treatment on its own has not significantly extended the survival of patients with GBM, upcoming studies should investigate the potential of combining ICI with various other immunotherapies such as CAR-T, oncolytic viruses, vaccines, or with alternative approaches like stereotactic surgery and localized chemotherapy [ 8 ] ( Figure 1 ).…”

“…Furthermore, oncolytic virotherapy can be combined with other treatment modalities, such as immunotherapy, to create synergistic effects [ 174 ]. By harnessing the immune system’s ability to recognize and attack cancer cells, this combination approach can enhance the overall antitumor response and improve long-term survival rates in patients with brain tumors [ 8 , 174 ]. DNX-2401, an oncolytic adenovirus, is designed to replicate selectively in cancer cells with certain genetic defects.…”

“…Standard care for newly diagnosed patients with GBM typically involves surgical resection followed by a combination of chemotherapy using temozolomide (TMZ) and radiotherapy [ 5 ]. However, recurrence often occurs within several months despite these treatments [ 6 , 7 , 8 ]. The rapid recurrence of GBM is attributed to its biological characteristics, primarily its invasive nature that makes complete removal through surgery, chemotherapy, or radiotherapy challenging [ 9 ].…”

Overcoming Barriers in Glioblastoma—Advances in Drug Delivery Strategies

“…At the same time, an improved drug distribution could result in increased toxicity, and tumor specificity becomes a more important factor to take into consideration. New trials studying CED in combination with tumor-specific therapeutic agents like nanoparticles or oncolytic viruses are, therefore, of special interest [ 124 ]. Desjardins et al reported the safety of intratumoral injection of the oncolytic polio/rhinovirus recombinant (RVSRIPO) that showed no neurovirulent potential but is specifically targeted to tumor cells and dendritic cells [ 125 ].…”