Current Understanding of Hypoxia in Glioblastoma Multiforme and Its Response to Immunotherapy

Cancers, Journal Year: 2022, Volume and Issue: 14(5), P. 1176 - 1176

Published: Feb. 24, 2022

Hypoxia is a hallmark of glioblastoma multiforme (GBM), the most aggressive cancer central nervous system, and associated with multiple aspects tumor pathogenesis. For example, hypoxia induces resistance to conventional therapies inhibits antitumor immune responses. Thus, targeting an attractive strategy for GBM therapy. However, traditional studies on have largely excluded system. Recently, critical role system in defense against tumors has become apparent, leading development effective immunotherapies numerous types. Critically, however, classified as “cold tumor” due poor improve responsiveness immunotherapies, improved understanding both function mediating responses within microenvironment needed. In this review, we discuss from clinical, pathological, immunological perspective.

Language: Английский

---

Immunotherapy of Primary Brain Tumors: Facts and Hopes

Clinical Cancer Research, Journal Year: 2018, Volume and Issue: 24(21), P. 5198 - 5205

Published: June 5, 2018

The field of cancer immunotherapy has made exciting progress for some types in recent years. However, failures late-phase clinical trials evaluating checkpoint blockade patients with glioblastoma (GBM) represent continued challenges brain immunotherapy. This is likely due to multiple factors including but not limited marked genetic and antigenic heterogeneity, relatively low mutational loads, paucity GBM-infiltrating T cells. We review ongoing studies targeting the molecules as monotherapy or combination other modalities, discuss mechanisms underlying unresponsiveness GBM single-modality approaches. also novel approaches that may promote T-cell responses overcome "cold tumor" status GBM, oncolytic viruses adoptive therapy. Clin Cancer Res; 24(21); 5198-205. ©2018 AACR.

Language: Английский

---

Glioblastoma multiforme: novel therapeutic targets

Expert Opinion on Therapeutic Targets, Journal Year: 2020, Volume and Issue: 24(7), P. 605 - 614

Published: May 12, 2020

Introduction The increasingly detailed genetic characterization of glioblastoma (GBM) has failed to translate into meaningful breakthroughs in treatment. This is likely be attributed molecular heterogeneity GBM. However, the understanding tumor microenvironment GBM become more refined and revealed a wealth therapeutic targets that may enable disruption angiogenesis or immunosuppression.Areas covered review discusses selective targeting tumor-intrinsic pathways, therapies target relevant preclinical studies their limitations. Relevant literature was derived from PubMed search encompassing 1989 2020.Expert opinion Despite appropriate engagement, attempts directly inhibit oncogenic pathways have yielded little success. presence redundant signaling allow for accumulation adaptive mutations development drug resistance. Subsequently, there been shift toward modulating pro-angiogenic, immunosuppressive non-transformed cells which includes endothelial cells, myeloid T are presumably genetically stable, less susceptible heterogeneity, easier target. approach offers highest potential breakthrough

Language: Английский

---

Current and Future Imaging Methods for Evaluating Response to Immunotherapy in Neuro-Oncology

Theranostics, Journal Year: 2019, Volume and Issue: 9(17), P. 5085 - 5104

Published: Jan. 1, 2019

Imaging plays a central role in evaluating responses to therapy neuro-oncology patients.The advancing clinical use of immunotherapies has demonstrated that treatment-related inflammatory mimic tumor growth via conventional imaging, thus spurring the development new imaging approaches adequately distinguish between pseudoprogression and progressive disease.To this end, an increasing number advanced techniques are being evaluated preclinical studies.These novel molecular will serve complement response assessments during immunotherapy.The goal these is provide definitive metrics at earlier time points inform treatment decisions, which potential improve patient outcomes.This review summarizes available immunotherapy regimens, criteria, current state-of-the-art approaches, groundbreaking strategies for future implementation evaluate anti-tumor immune applications.

Language: Английский

---

The transformative potential of mRNA vaccines for glioblastoma and human cancer: technological advances and translation to clinical trials

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 27, 2024

Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments control infectious disease, notably their pivotal role in combating COVID-19 pandemic. This review focuses on fundamental aspects development vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, – highlighting key technological advances. The recent, promising success personalized against pancreatic melanoma illustrates potential value other intractable, immunologically resistant, solid tumors, such glioblastoma, well synergies with a combinatorial, immunotherapeutic approach. impact progress human cancer, including head neck bladder are reviewed, lessons learned from first-in-human CAR-T cell, DNA dendritic cell targeting glioblastoma. Going forward, roadmap is provided transformative advance immunotherapy, particular focus opportunities challenges current landscape glioblastoma immunotherapy gene therapy reviewed an eye combinatorial approaches harnessing RNA science. Preliminary preclinical clinical data supports concept that could be viable, novel approach prolong survival patients

Language: Английский

---

Enterovirus A71 Oncolysis of Malignant Gliomas

Molecular Therapy, Journal Year: 2020, Volume and Issue: 28(6), P. 1533 - 1546

Published: April 14, 2020

Malignant gliomas, the most lethal type of primary brain tumor, continue to be a major therapeutic challenge. Here, we found that enterovirus A71 (EV-A71) can developed as novel oncolytic agent against malignant gliomas. EV-A71 preferentially infected and killed glioma cells relative normal glial cells. The virus receptor human scavenger class B, member 2 (SCARB2), phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)-mediated cell death were involved in EV-A71-induced oncolysis. In mice with implanted subcutaneous intraneoplastic inoculation caused significant tumor growth inhibition. Furthermore, bearing intracranial orthotopic substantially prolonged survival. By insertion brain-specific microRNA-124 (miR124) response elements into viral genome, improved specificity therapy by reducing its neurotoxicity while maintaining replication potential capacity Our study reveals is potent gliomas may have role treating this clinical setting.

Language: Английский

---

Interleukin 6 and cancer resistance in glioblastoma multiforme

Neurosurgical Review, Journal Year: 2024, Volume and Issue: 47(1)

Published: Sept. 5, 2024

Language: Английский

---

Molecular imaging and advanced MRI findings following immunotherapy in patients with brain tumors

Expert Review of Anticancer Therapy, Journal Year: 2019, Volume and Issue: 20(1), P. 9 - 15

Published: Dec. 16, 2019

Introduction: Currently, immunotherapy using vaccination strategies or oncolytic virus approaches, cell-based immunotherapy, and the blockade of immune checkpoints are under evaluation in patients with brain cancer. Here we summarize clinically significant imaging findings such as treatment-related changes detected by advanced neuroimaging techniques following most suitable options currently used neuro-oncology. We, furthermore, provide an overview how these may help to overcome shortcomings standard MRI assessment follow-up cancer.Areas covered: The current literature on for field tumors, a focus gliomas metastases is summarized.Expert commentary: Data suggest that parameters primarily derived from amino acid PET, diffusion- perfusion-weighted MRI, MR spectroscopy particularly helpful treatment response valuable information differentiation treatment-induced actual tumor progression various approaches.

Language: Английский

---

An immune-competent, replication-permissive Syrian Hamster glioma model for evaluating Delta-24-RGD oncolytic adenovirus

Neuro-Oncology, Journal Year: 2021, Volume and Issue: 23(11), P. 1911 - 1921

Published: May 29, 2021

Oncolytic adenoviruses are promising new treatments against solid tumors, particularly for glioblastoma (GBM), and preclinical models required to evaluate the mechanisms of efficacy. However, due species selectivity adenovirus, there is currently no single animal model that supports viral replication, tumor oncolysis, a virus-mediated immune response. To address this gap, we took advantage Syrian hamster develop first intracranial glioma both adenovirus replication-permissive immunocompetent.We generated stem-like cells (hamGSCs) by transforming neural stem with hTERT, simian virus 40 large T antigen, h-RasV12. Using guide-screw system, an in hamster. The efficacy oncolytic Delta-24-RGD was assessed survival studies, tumor-infiltrating lymphocytes (TILs) were evaluated flow cytometry.In vitro, hamGSCs supported replication susceptible mediated cell death. In vivo, consistently developed into highly proliferative tumors resembling high-grade glioma. Flow cytometric analysis gliomas revealed significantly increased T-cell infiltration infected indicative activation. Treating tumor-bearing hamsters led compared treated phosphate buffered saline (PBS).This adenovirus-permissive, immunocompetent overcomes limitations previous systems provides novel platform study interactions between cells, host adenoviral therapy; understanding which will be critical implementing clinic.

Language: Английский

---

Viral Therapy Gets Personal: A Potential Gene Signature to Predict Susceptibility to Measles Virus Oncolysis

JNCI Journal of the National Cancer Institute, Journal Year: 2018, Volume and Issue: 110(10), P. 1139 - 1140

Published: March 12, 2018

Language: Английский

---