Adoptive Cell Therapy: A Novel and Potential Immunotherapy for Glioblastoma

Wang, Jingyu; Shen, Fang; Yao, Ying; Wang, Lin-Lin; Zhu, Yixuan; Hu, Jue

doi:10.3389/fonc.2020.00059

Cited by 30 publications

(28 citation statements)

References 132 publications

(143 reference statements)

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“…The clinical trials, ClinicalTrials.gov NCT identifiers: NCT02208362, NCT01454596, NCT01109095, targeting IL-13Rα2, EGFRvIII, and HER2, respectively, provide useful insights on the immunotherapeutic ability of CAR T cells against gliomas (Migliorini et al, 2018). These trials showed the CAR T cells': low toxicity, moderate ability to traffic to the glioma microenvironment, limited ability to target glioma cells, and inconsistent results in increasing overall survival (Migliorini et al, 2018;Akhavan et al, 2019;Wang et al, 2020). For example, HER2-specific CAR T cells, in the NCT01109095 NCT00648739 Samalizumab Glioblastoma Recruiting Wright et al (2000), Gorczynski et al (2000), Wright et al (2003) trial, were used to treat 17 patients with progressive GBM (Ahmed et al, 2017).…”

Section: Car-t Cellsmentioning

confidence: 99%

Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments

et al. 2021

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Gliomas are one of the most lethal types of cancers accounting for ∼80% of all central nervous system (CNS) primary malignancies. Among gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas.

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Section: Car-t Cellsmentioning

confidence: 99%

Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments

et al. 2021

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“…ACTs using autologous TILs and CAR-T cells are the most prevalent strategy being explored in GBM, as evidenced by the number of completed or running clinical trials [ 272 ]. ACT by autologous lymphocytes relies on MHC-restricted tumor antigen recognition via T cell receptors (TCRs) [ 273 ]. It has also been demonstrated that TILs harvested from GBM patients can recognize and kill autologous tumor cells [ 274 ], but recent studies reveal that not all TILs are tumor-specific.…”

Section: Treatments In Developmentmentioning

confidence: 99%

“…CAR-T cells are engineered to directly recognize tumor-specific antigens (e.g., EGFR vIII , HER2, IL-13Rα2, EphA2.) in an MHC-independent manner [ 273 ]. As an example, single intravenous infusion of CAR-T cells redirected to EGFR vIII antigen in patients with recurrent GBM lead to the loss of EGFR vIII in 5/7 patients [ 278 ].…”

Section: Treatments In Developmentmentioning

confidence: 99%

Pathogenetic Features and Current Management of Glioblastoma

Nguyen

Guz-Montgomery

Lowe

et al. 2021

Cancers

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Glioblastoma (GBM) is the most common form of primary malignant brain tumor with a devastatingly poor prognosis. The disease does not discriminate, affecting adults and children of both sexes, and has an average overall survival of 12–15 months, despite advances in diagnosis and rigorous treatment with chemotherapy, radiation therapy, and surgical resection. In addition, most survivors will eventually experience tumor recurrence that only imparts survival of a few months. GBM is highly heterogenous, invasive, vascularized, and almost always inaccessible for treatment. Based on all these outstanding obstacles, there have been tremendous efforts to develop alternative treatment options that allow for more efficient targeting of the tumor including small molecule drugs and immunotherapies. A number of other strategies in development include therapies based on nanoparticles, light, extracellular vesicles, and micro-RNA, and vessel co-option. Advances in these potential approaches shed a promising outlook on the future of GBM treatment. In this review, we briefly discuss the current understanding of adult GBM’s pathogenetic features that promote treatment resistance. We also outline novel and promising targeted agents currently under development for GBM patients during the last few years with their current clinical status.

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“…The purpose of cell-based therapy is to enhance the anti-tumor activity of patient-derived T cells by engineering them to express either a chimeric antigen receptor (CAR) or a T cell receptor (TCR) targeting specific tumor antigens. However, this section will focus primarily on CAR-T cell therapy [ 58 ]. Unlike CAR-T cells, TCR-modified T cells rely on major histocompatibility class (MHC) peptide presentation, which GBM can suppress, thereby evading MHC-restricted T cell recognition and rendering TCR-modified T cells incapable of recognizing tumor-associated antigens (TAAs) [ 59 ].…”

Section: Recent Advances In Immunotherapymentioning

confidence: 99%

Current Advances in Immunotherapy for Glioblastoma

et al. 2021

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Purpose of Review This review seeks to inform oncology clinicians and researchers about the development of novel immunotherapies for the treatment of glioblastoma. An enumeration of ongoing and recently completed clinical trials will be discussed with special attention given to current technologies implemented to overcome central nervous system–specific challenges including barriers to the peripheral immune system, impaired antigen presentation, and T cell dysfunction. Recent Findings The success of immunotherapy in other solid cancers has served as a catalyst to explore its application in glioblastoma, which has limited response to other treatments. Recent developments include multi-antigen vaccines that seek to overcome the heterogeneity of glioblastoma, as well as immune checkpoint inhibitors, which could amplify the adaptive immune response and may have promise in combinatorial approaches. Additionally, oncolytic and retroviruses have opened the door to a plethora of combinatorial approaches aiming to leverage their immunogenicity and/or ability to carry therapeutic transgenes. Summary Treatment of glioblastoma remains a serious challenge both with regard to immune-based as well as other therapeutic strategies. The disease has proven to be highly resistant to treatment due to a combination of tumor heterogeneity, adaptive expansion of resistant cellular subclones, evasion of immune surveillance, and manipulation of various signaling pathways involved in tumor progression and immune response. Immunotherapeutics that are efficacious in other cancer types have unfortunately not enjoyed the same success in glioblastoma, illustrating the challenging and complex nature of this disease and demonstrating the need for development of multimodal treatment regimens utilizing the synergistic qualities of immune-mediated therapies.

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Adoptive Cell Therapy: A Novel and Potential Immunotherapy for Glioblastoma

Cited by 30 publications

References 132 publications

Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments

Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments

Pathogenetic Features and Current Management of Glioblastoma

Current Advances in Immunotherapy for Glioblastoma

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