Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults

Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite standard therapies, including resection and chemoradiation, recurrence is virtually inevitable. Current treatment for recurrent glioblastoma (rGBM) is rapidly evolving, and emerging therapies aimed at targeting primary GBM are often first tested in rGBM to demonstrate safety and feasibility, which, in recent years, has primarily been in the form of immunotherapy. The purpose of this review is to highlight progress in clinical trials of immunotherapy for rGBM, including immune checkpoint blockade, oncolytic virotherapy, chimeric antigen receptor (CAR) T-cell therapy, cancer vaccine and immunotoxins. Three independent reviewers covered literature, published between the years 2000 and 2022, in various online databases. In general, the efficacy of immunotherapy in rGBM remains uncertain, and is limited to subsets/small cohorts of patients, despite demonstrating feasibility in early-stage clinical trials. However, considerable progress has been made in understanding the mechanisms that may preclude rGBM patients from responding to immunotherapy, as well as in developing new approaches/combination strategies that may inspire optimism for the utility of immunotherapy in this devastating disease. Continued trials are necessary to further assess the best therapeutic avenues and ascertain which treatments might benefit each patient individually.

Designing Gold Nanoparticles for Precise Glioma Treatment: Challenges and Alternatives

“…Glioblastoma multiforme (GBM) is a grade IV glioma arising from glial and neuronal cells. It is the most common malignant tumor in the central nervous system [ 124 ]. The location of GBM is dependent upon the amount of white matter present.…”

“…The presumed progression of tumor cells along neuronal fibers without macroscopic changes leads to a failure to achieve clear surgical margins [ 17 , 125 ]. However, this clinical standard and the multitudes of novel treatments currently in or that have gone through clinical trials for safety and efficacy face several hurdles, including tumor heterogeneity, the BBB, and tumor complexity [ 124 ]. One experimental therapy which cleared trials and is now included in the standard of care is the use of tumor-treating fields, which have improved survival in GBM patients [ 129 ].…”

Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level

“…Among these, LGG is an inert precursor of GBM, which usually remains unchanged for a long time and its prognosis is better proofread (3)(4)(5)(6). In contrast, ndGBM and rGBM have a relatively poor prognosis (7,8). Currently, multimodal therapies, such as maximal surgical resection, radiotherapy, and temozolomide adjuvant chemotherapy, are considered the primary treatment modalities for GBM.…”