Advanced Immunotherapy Approaches for Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is the most aggressive primary central nervous system (CNS) tumor, and treatment for GBM is regarded as the most challenging task in clinical oncology. Although multiple treatments are available, including surgery, chemotherapy, and radiotherapy, these conventional therapies barely improve the functional prognosis and life quality of patients with glioblastoma. Immunotherapy, has become a promising approach for treating GBM because of the ability to overcome the blood-brain barrier (BBB) and complicated unique tumor immune microenvironment. Developing an efficient immunotherapy for GBM requires understanding the glioblastoma immune microenvironment; accordingly, this study begins by summarizing this and what it indicates for the development of immunological effects. Then current immunotherapy management for GBM and advanced studies including checkpoint inhibitors, cell vaccines, and extracellular vesicle-based immunotherapy is reviewed. Because monotherapies are inadequate for treating GBM, combinational GBM immunotherapy with other classical cancer therapies, especially chemo-immunotherapy, radiotherapy-immunotherapy, and the combination of gene therapy and immunotherapy, is introduced and discussed. The recent progress introduced in this review suggests that cancer immunotherapy and its combinatory therapies are highly promising treatment modalities for glioblastoma patients. However, systematical and in-depth investigations are required to improve the efficacy of GBM immunotherapy for future clinical translation.

Multi‐ligand functionalized blood‐to‐tumor sequential targeting strategies in the field of glioblastoma nanomedicine

“…Nonetheless, over time, TTFs have gained great acceptance, not only because of the above‐mentioned OS and PFS numbers, but also due to an increase in the 5‐year survival of GBM patients from approximately 5%–13% compared to the SOC arm (Stupp et al, 2017). Other treatment modalities, such as immunotherapy (Ma et al, 2021), gene therapy (Yoo et al, 2021) and phototherapy (Li et al, 2022) are emerging as promising therapeutic approaches for GBM.…”

“…Active targeting strategies rely on the interaction between ligand (nanomedicine surface) and receptor (tissue of interest), promoting higher accumulation of cargos loaded into the nanosystems at the targeted site and, thus, an ameliorated therapeutic efficacy. Due to the privileged anatomical location of GBM, the brain, access of therapeutics is hindered by the presence of the most important of all gateways and difficult‐to‐permeate blood‐brain barrier (BBB) (Ma et al, 2021). Moreover, it is still a grand challenge to endow nanomedicines with the ability to target invading tumor cells in the brain, post‐BBB crossing.…”

Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy

“…Exosomes are nano-sized lipid vesicles secreted from living cells, ranging from 30 to 200 nm, present in cell culture medium and other biological fluids [ 136 , 137 ]. Exosomes are promising candidates for drug delivery platforms because of their high biocompatibility, blood–brain barrier (BBB) crossing capability, and low immunogenicity [ 138 , 139 ]. Exosomes carry various proteins and nucleic acids, reflecting their cell of origin; thus, the choice of donor cell type for exosomes is important if utilizing exosomes in drug delivery and diagnosis systems [ 140 , 141 ].…”

Integrative analysis of single-cell transcriptomics reveals age-associated immune landscape of glioblastoma

“…GBM is an aggressive brain cancer with a high incidence rate of 32 per 1,000,000 per year ( 1 ). GBM is hard for radical cures surgically and is invalid to radiotherapy and chemotherapy in clinic ( 2 , 3 ). Patients died by rapid deterioration and shortage of effective medicines.…”