Current Advances in Immunotherapy for Glioblastoma Multiforme and Future Prospects

Abstract

Glioblastoma is the most frequent and malignant type of brain tumor. It has a reputation for being resistant to current treatments, and the prognosis is still bleak. Immunotherapies have transformed the treatment of a variety of cancers, and they provide great hope for glioblastoma, although they have yet to be successful. The justification for immune targeting of glioblastoma and the obstacles that come with treating these immunosuppressive tumors are reviewed in this paper. Cancer vaccines, oncolytic viruses (OVs), checkpoint blockade medications, adoptive cell transfer (ACT), chimeric antigen receptor (CAR) T-cells, and nanomedicine-based immunotherapies are among the novel immune-targeting therapies researched in glioblastoma. Key clinical trial outcomes and current trials for each method are presented from a clinical standpoint. Finally, constraints, whether biological or due to trial design, are discussed, along with solutions for overcoming them. In glioblastoma, proof of efficacy for immunotherapy approaches has yet to be demonstrated, but our rapidly growing understanding of the disease's biology and immune microenvironment, as well as the emergence of novel promising combinatorial approaches, may allow researchers to finally meet the medical need for patients with glioblastoma multiforme (GBM).

Immunotherapy in glioblastoma treatment: Current state and future prospects

“…As aforementioned, the cooperation of the innate and adaptive immune systems is crucial in oncolytic virotherapy response, and matching it with other immunotherapy strategies such as checkpoint inhibitors increases the immunological response and tumor regression[ 140 - 142 ].…”

“…However, the results were not as significant as expected in survival and remission rate, in human trials[ 146 ]. Besides that many adverse effects have been found such as seizures, edema, thrombocytopenia and pulmonary embolism, and these complications when coupled with the fact that not all GBM patients express EGFRvIII, become a limitation for this therapy, since not all patients could use this vaccine[ 140 ].…”

“…In this sense, the various ongoing studies and clinical trials may provide favorable outcomes in expanding the use of these therapies in the near future, and, given the potential to manipulate or enhance the immune system apparatus to attack and kill tumor cells, immunotherapy has enlightened and generated a lot of excitement in the treatment of GBM. However, so far, there are some limiting factors that hinder the applicability of immunotherapy in the treatment of glioblastoma, whether related to individual anatomical and immunological factors or to routes of administration and adverse effects[ 140 - 142 ].…”

“…In order to increase the therapeutic effectiveness of the current immunotherapy approaches, various strategies have been developed to increase drug penetration and decrease the occurrence of adverse effects. Of note, we highlight (1) the use of combined therapies, for synergistic action[ 153 ]; (2) targeted drug delivery, which increases pharmacokinetic properties and reduces toxicity[ 79 ]; and (3) intrathecal administration, to overcome the blood-brain barrier[ 140 - 142 ].…”

Development of therapeutic antibodies for the treatment of diseases

“…Nivolumab, an anti-PD-1 mAb that was also approved for use by the US FDA in 2014 as well, was assessed as a treatment for recurrent or metastatic squamous-cell carcinoma of the head and neck [ 20 ], advanced renal-cell carcinoma [ 38 ], and nonsquamous NSCLC [ 39 ]. Additionally, it works on Glioblastoma Multiforme since the PD-L1 protein is abundant on its surface [ 40 ]. A lot of randomized clinical trials indicated that NSCLC patients who were treated combination with nivolumab with pembrolizumab showed higher overall survival than those treated with docetaxel [ 41 ].…”