A review of glioblastoma immunotherapy

Medikonda, Ravi; Dunn, Gavin P.; Rahman, Maryam; Fecci, Peter E.; Lim, Michael

doi:10.1007/s11060-020-03448-1

Cited by 206 publications

(182 citation statements)

References 115 publications

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“…GBM is also a remarkably heterogeneous tumor that facilitates immune escape, which may be the largest obstacle (13,76,77). According to the gene expression analysis, GBM can be divided into four subtypes: typical, neuroural, proneural, and mesocytic (78).…”

Section: Heterogeneity Of Gbm and Antigen Escapementioning

confidence: 99%

“…The purpose of tumor immunotherapy is to overcome the immune resistance of tumor cells in order to treat the tumor. Immunotherapy includes vaccines, oncolytic virus therapies, checkpoint blockade, and adoptive T cells (13). Tumor immunotherapy has rapidly evolved in recent years and has shown promising results in a variety of tumors such as lung cancer (14), kidney cancer (15), and melanoma (16).…”

Section: Introductionmentioning

confidence: 99%

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Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future

et al. 2020

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Glioblastoma (GBM) is a highly aggressive glioma with an extremely poor prognosis after conventional treatment. Recent advances in immunotherapy offer hope for these patients with incurable GBM. Our present review aimed to provide an overview of immunotherapy for GBM, especially chimeric antigen receptor T-cell (CAR T) therapy. CAR T-cell immunotherapy, which involves the engineering of T cells to kill tumors by targeting cell surface-specific antigens, has been successful in eliminating B-cell leukemia by targeting CD19. IL-13Ra2, EGFRvIII, and HER2-targeted CAR T cells have shown significant clinical efficacy and safety in phase 1 or 2 clinical trials conducted in patients with GBM; these findings support the need for further studies to examine if this therapy can ultimately benefit this patient group. However, local physical barriers, high tumor heterogeneity, and antigen escape make the use of CAR T therapy, as a treatment for GBM, challenging. The potential directions for improving the efficacy of CAR T in GBM are to combine the existing traditional therapies and the construction of multi-target CAR T cells.

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Section: Heterogeneity Of Gbm and Antigen Escapementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future

et al. 2020

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“…However, the trial is currently on hold, and the final analysis with reasons for suspension is pending. [ 52,190–192 ] Similar phase I/II trials aimed at priming dendritic cells include pulsation with GBM tumor lysate (NCT03360708) or cytomegalovirus antigens (NCT00639639, NCT02465268) are ongoing. [ 193–195 ] Other vaccine‐based approaches in ongoing clinical trials utilize direct injection of immunostimulatory peptides such as telomerase‐derived (NCT04280848) or heat shock protein‐derived (NCT027225512) peptides in order to prime the immune system.…”

Section: Drug‐loaded Nanoparticlesmentioning

confidence: 99%

“…It is evident that combinatorial approaches that target multiple immune mechanisms will be critical in the design of future immune‐based nanomedicine strategies given the outcomes of recent clinical trials. [ 52,195 ] Furthermore, immune compartments such as the complement system are relatively untapped in nanomedicine and opportunities exist to develop nanotherapeutic targets to better enhance innate and adaptive immune system cross‐talk and activity in GBM. [ 199 ]…”

Section: Drug‐loaded Nanoparticlesmentioning

confidence: 99%

Nanomedicine Revisited: Next Generation Therapies for Brain Cancer

Bhargav

Mondal

Garcia

et al. 2020

Advanced Therapeutics

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Brain cancer persists as a difficult-to-treat condition. In particular, metastatic brain cancer and malignant primary brain tumors such as glioblastoma (GBM) are among the most deadly and still carry a dismal prognosis despite current standard of care with surgery and chemo-radiation. Recent advances in nanotechnology have led to innovative nanomedicine strategies for the treatment of brain cancers and specifically for GBM. These strategies represent promising alternative or adjunctive therapies for conventional treatment modalities and are increasingly designed to target specific cell types such as brain tumor-initiating cells and immune cells. This review provides an update on emerging insights into these nanomedicine strategies with a focus on nanoparticles as tools that facilitate 1) drug delivery 2) gene therapy, and 3) engineered-cellular therapy for GBM and future directions for brain cancer treatment.

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“…The average survival in GBM without treatment is three months and with current treatments it is 12–19 months [ 9 , 10 ]. Standard treatment includes surgery, radiotherapy, and chemotherapy [ 9 ]. Temozolomide (TMZ) is the gold-standard chemotherapy used in GBM due to its high permeability to the blood–brain barrier (BBB).…”

Section: Introductionmentioning

confidence: 99%

Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma

Jin

Mao

Chen

et al. 2021

Cancers

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Brain tumors comprise different types of malignancies, most of which are originated from glial cells. Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with a poor response to conventional therapies and dismal survival rates (15 months) despite multimodal therapies. The development of immunotherapeutic strategies seems to be necessary to enhance the overall survival of GBM patients. So far, the immunotherapies applied in GBM had promising results in the primary phases of clinical trials but failed to continue their beneficial effects in later phases. GBM-microenvironment (GME) is a heterogenic and rigorously immunosuppressive milieu wrapping by an impenetrable blood-brain barrier. Hence, in-depth knowledge about the dominant immunosuppressive mechanisms in the GME could foster GBM immunotherapy. Recently, the adenosinergic pathway (AP) is found to be a major player in the suppression of antitumor immune responses in the GME. Tumor cells evolve to metabolize pro-inflammatory ATP to anti-inflammatory adenosine. Adenosine can suppress immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in GBM showed promising results in reinvigorating antitumor responses, overriding chemoresistance, and increasing survival. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. We suggest that future clinical studies should consider this pathway in their combination therapies along with other immunotherapeutic approaches.

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A review of glioblastoma immunotherapy

Cited by 206 publications

References 115 publications

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future

Nanomedicine Revisited: Next Generation Therapies for Brain Cancer

Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma

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