CAR-based therapeutic targets in pediatric high-grade glioma DOI Creative Commons

Myrthe M.M.R. Griffioen,

Dennis S. Metselaar

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract High-grade glioma (HGG) patients have a dismal prognosis, due to lack of effective treatments. In order change the fate HGG and decrease current treatment-related side effects, therapy focus has shifted in past years immunotherapy, such as chimeric antigen receptor (CAR)-based Recent developments CAR-based show promising results adult patients, first clinical trials for pediatric with are progress. However, there significant differences between (pHGG) their counterparts, including composition tumor immune microenvironment (TIME), which strongly influences CAR treatment responsiveness. Therefore, we here provide systematic overview therapeutic targets pHGG entities, focusing on preclinical research, comparing them glioma. We conclude that target expression, TIME toxicities vary across entities differ from HGG, suggests need more tailored immunotherapeutic approaches pHGG. Overall, roadmap future development strategies who desperate novel therapies. Graphical abstract The number potential glioblastoma CAR: Chimeric receptor; pHGG: high-grade glioma; DHG: H3 G34-mutant diffuse hemispheric DMG: K27-altered midline PFA: posterior fossa ependymoma type A. Image was created Biorender.com .

Language: Английский

Neutrophil generation from hematopoietic progenitor cells and induced pluripotent stem cells (iPSCs): potential applications DOI
Abdollah Jafarzadeh,

Marzieh Motaghi,

Sanand Kumar Patra

et al.

Cytotherapy, Journal Year: 2024, Volume and Issue: 26(8), P. 797 - 805

Published: March 30, 2024

Language: Английский

Citations

7
The transformative potential of mRNA vaccines for glioblastoma and human cancer: technological advances and translation to clinical trials DOI Creative Commons
Iulia Tapescu, Peter J. Madsen, Pedro R. Löwenstein

et al.

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

Citations

4
Strategies to overcome tumor microenvironment immunosuppressive effect on the functioning of CAR-T cells in high-grade glioma DOI Creative Commons

Julia Zarychta,

Adrian Kowalczyk,

Anna Marszołek

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 1, 2024

Despite significant progress in the treatment of some types cancer, high-grade gliomas (HGGs) remain a clinical problem. In case glioblastoma (GBM), most common solid tumor central nervous system adults, average survival time from diagnosis is only 15-18 months, despite use intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by Food and Drug Administration for certain hematologic malignancies, are new, promising therapeutic option. However, efficacy CAR-T cells tumors lower due to immunosuppressive microenvironment (TME). Reprogramming TME toward pro-inflammatory phenotype therefore seems particularly important because it may allow increasing effectiveness therapy tumors. The following literature review aims present results preclinical studies showing possibilities improving GBM reprogramming phenotype. It be achievable thanks synergistic combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well supporting crossing blood-brain barrier, normalizing impaired angiogenesis TME, effector functions cytokine signaling blocking/knocking out T-cell modulating microRNA expression. modified this way could lead longer patients HGG inducing an endogenous anti-tumor response.

Language: Английский

Citations

3
β-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization DOI Open Access
Yimin Yang,

Xuling Luo,

Yaling Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117074 - 117074

Published: July 6, 2024

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of β-mangostin, xanthone derivative obtained from mangosteen fruit. This investigated role β-mangostin on microglia in glioma microenvironment evaluated efficacy combined anti-PD-1 antibody (αPD-1) glioma-bearing mice. The results showed that, attenuated M2 polarization BV2 cells promoted M1-related interleukin (IL)-1β IL-6 secretion, thereby inhibiting invasion. In addition, improved anti-glioma effects αPD-1 increased CD8

Language: Английский

Citations

1
Association of RAN and RANBP2 Gene Polymorphisms With Glioma Susceptibility in Chinese Children DOI Creative Commons
Qianru Lin, Wei Chen,

Jiating Tan

et al.

Cancer Reports, Journal Year: 2024, Volume and Issue: 7(7)

Published: July 1, 2024

Glioma is the most prevalent pediatric central nervous system malignancy. RAN, member RAS oncogene family (RAN), a key signaling molecule that regulates polymerization of microtubules during mitosis. RAN binding protein 2 (RANBP2) involved in DNA replication, mitosis, metabolism, and tumorigenesis. The effects RANBP2 gene polymorphisms on glioma susceptibility Chinese children are currently unknown.

Language: Английский

Citations

0
CAR-based therapeutic targets in pediatric high-grade glioma DOI Creative Commons

Myrthe M.M.R. Griffioen,

Dennis S. Metselaar

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract High-grade glioma (HGG) patients have a dismal prognosis, due to lack of effective treatments. In order change the fate HGG and decrease current treatment-related side effects, therapy focus has shifted in past years immunotherapy, such as chimeric antigen receptor (CAR)-based Recent developments CAR-based show promising results adult patients, first clinical trials for pediatric with are progress. However, there significant differences between (pHGG) their counterparts, including composition tumor immune microenvironment (TIME), which strongly influences CAR treatment responsiveness. Therefore, we here provide systematic overview therapeutic targets pHGG entities, focusing on preclinical research, comparing them glioma. We conclude that target expression, TIME toxicities vary across entities differ from HGG, suggests need more tailored immunotherapeutic approaches pHGG. Overall, roadmap future development strategies who desperate novel therapies. Graphical abstract The number potential glioblastoma CAR: Chimeric receptor; pHGG: high-grade glioma; DHG: H3 G34-mutant diffuse hemispheric DMG: K27-altered midline PFA: posterior fossa ependymoma type A. Image was created Biorender.com .

Language: Английский

Citations

0