scholarly journals Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1294
Author(s):  
Yogesh R. Suryawanshi ◽  
Autumn J. Schulze
Keyword(s):  
Immune Responses ◽  
Malignant Glioma ◽  
Blood Brain Barrier ◽  
Tumor Heterogeneity ◽  
Checkpoint Inhibitors ◽  
Oncolytic Viruses ◽  
Brain Barrier ◽  
Current Status ◽  
Blood Brain ◽  
Federal Authority

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood–brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood–brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

scholarly journals Genetics and sex influence peripheral and central innate immune responses and blood-brain barrier integrity

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205769 ◽  
Author(s):  
Michelle A. Erickson ◽  
W. Sandy Liang ◽  
Elizabeth G. Fernandez ◽  
Kristin M. Bullock ◽  
Jarl A. Thysell ◽  
...  
Keyword(s):  
Immune Responses ◽  
Blood Brain Barrier ◽  
Innate Immune ◽  
Brain Barrier ◽  
Innate Immune Responses ◽  
Barrier Integrity ◽  
Sex Influence ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

The Current Status of Multiple Sclerosis Intra-Blood-Brain-Barrier IgG Synthesis

1984 ◽  
Vol 436 (1 Multiple Scle) ◽  
pp. 52-67 ◽  
Author(s):  
WALLACE W. TOURTELLOTTE ◽  
MICHAEL J. WALSH ◽  
ROBERT W. BAUMHEFNER ◽  
SUSAN M. STAUGAITIS ◽  
PAUL SHAPSHAK
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Current Status ◽  
Blood Brain ◽  
Igg Synthesis

Non-invasive transferrin targeted nanovesicles sensitize resistant glioblastoma multiforme tumors and improve survival in orthotopic mouse models

Nanoscale ◽  
2021 ◽  
Author(s):  
Puja Sandbhor ◽  
Jayant Goda ◽  
Bhabani Mohanty ◽  
Pradip Chaudhari ◽  
Shilpee Dutt ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Clinical Outcomes ◽  
Blood Brain Barrier ◽  
Mouse Models ◽  
Tumor Heterogeneity ◽  
Brain Barrier ◽  
Therapeutic Regimen ◽  
Non Invasive ◽  
Blood Brain

The blood–brain barrier (BBB) and tumor heterogeneity have resulted in abysmally poor clinical outcomes in glioblastoma (GBM) with the standard therapeutic regimen.

scholarly journals Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna Galstyan ◽  
Janet L. Markman ◽  
Ekaterina S. Shatalova ◽  
Antonella Chiechi ◽  
Alan J. Korman ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Brain Tumor ◽  
Blood Brain Barrier ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Brain Barrier ◽  
Systemic Delivery ◽  
Blood Brain

AbstractBrain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross blood–brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB and activation of local brain anti-tumor immune response. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of tumor-targeted polymer-conjugated checkpoint inhibitors as an effective GBM treatment via activation of both systemic and local privileged brain tumor immune response.

scholarly journals Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance

2021 ◽  
Vol 22 (23) ◽  
pp. 12654
Author(s):  
Francesca Mo ◽  
Alessia Pellerino ◽  
Riccardo Soffietti ◽  
Roberta Rudà
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Phase 1 ◽  
Brain Barrier ◽  
Convection Enhanced Delivery ◽  
Cell Lung Carcinoma ◽  
Blood Brain

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1–2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.

scholarly journals Nano immunoconjugates crossing blood-brain barrier activate local brain tumor immune system for glioma treatment

2018 ◽  
Author(s):  
Anna Galstyan ◽  
Antonella Chiechi ◽  
Alan J. Korman ◽  
Tao Sun ◽  
Liron L. Israel ◽  
...  
Keyword(s):  
Immune Response ◽  
Brain Tumor ◽  
Blood Brain Barrier ◽  
T Regulatory Cells ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Brain Barrier ◽  
Blood Brain ◽  
Local Brain

AbstractTreatment of brain gliomas with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross the blood-brain barrier (BBB). We describe a new generation of nano immunoconjugates (NICs) developed on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 and/or a-PD-1 for delivery across the BBB and activation of local brain anti-tumor immune response in glioma-bearing mice. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) resulted in an increase of CD8+ T-cells with a decrease of T regulatory cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with combination of NICs was significantly longer compared to animals treated by single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of nanopolymer-conjugated checkpoint inhibitors as an effective treatment of GBM via activation of both systemic and local brain tumor immune response.

scholarly journals Established and Emerging Strategies for Drug Delivery Across the Blood-Brain Barrier in Brain Cancer

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 245 ◽  
Author(s):  
Alessandro Parodi ◽  
Magdalena Rudzińska ◽  
Andrei Deviatkin ◽  
Surinder Soond ◽  
Alexey Baldin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Cancer ◽  
Nervous Tissue ◽  
Vascular Wall ◽  
Brain Barrier ◽  
Current Status ◽  
Working Mechanism ◽  
Blood Brain

Brain tumors are characterized by very high mortality and, despite the continuous research on new pharmacological interventions, little therapeutic progress has been made. One of the main obstacles to improve current treatments is represented by the impermeability of the blood vessels residing within nervous tissue as well as of the new vascular net generating from the tumor, commonly referred to as blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), respectively. In this review, we focused on established and emerging strategies to overcome the blood-brain barrier to increase drug delivery for brain cancer. To date, there are three broad strategies being investigated to cross the brain vascular wall and they are conceived to breach, bypass, and negotiate the access to the nervous tissue. In this paper, we summarized these approaches highlighting their working mechanism and their potential impact on the quality of life of the patients as well as their current status of development.

scholarly journals Commentary on human pluripotent stem cell-based blood–brain barrier models

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ethan S. Lippmann ◽  
Samira M. Azarin ◽  
Sean P. Palecek ◽  
Eric V. Shusta
Keyword(s):  
Stem Cell ◽  
Blood Brain Barrier ◽  
Pluripotent Stem Cells ◽  
Research Community ◽  
Brain Barrier ◽  
Current Status ◽  
Human Pluripotent Stem Cell ◽  
Blood Brain ◽  
Published Evidence ◽  
Negative Attributes

Abstract In 2012, we provided the first published evidence that human pluripotent stem cells could be differentiated to cells exhibiting markers and phenotypes characteristic of the blood–brain barrier (BBB). In the ensuing years, the initial protocols have been refined, and the research community has identified both positive and negative attributes of this stem cell-based BBB model system. Here, we give our perspective on the current status of these models and their use in the BBB community, as well as highlight key attributes that would benefit from improvement moving forward.

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