scholarly journals Combined treatment modality in pediatric infratentorial midline high‐grade glioma can lead to long‐term survival: A case study and review of literature

Author(s):  
Saroj Das Majumdar ◽  
Sovan Sarang Dhar ◽  
Chinzah Lalsangzuala ◽  
Rabi Sahu ◽  
Suvendu Purkait ◽  
...  
2011 ◽  
Vol 104 (9) ◽  
pp. 1365-1371 ◽  
Author(s):  
Y R Lawrence ◽  
M Wang ◽  
A P Dicker ◽  
D Andrews ◽  
W J Curran ◽  
...  

2005 ◽  
Vol 12 (4) ◽  
pp. 389-398 ◽  
Author(s):  
Stanley S. Stylli ◽  
Andrew H. Kaye ◽  
Lachlan MacGregor ◽  
Megan Howes ◽  
Priya Rajendra

Gene Therapy ◽  
2004 ◽  
Vol 11 (22) ◽  
pp. 1648-1658 ◽  
Author(s):  
S Harrow ◽  
V Papanastassiou ◽  
J Harland ◽  
R Mabbs ◽  
R Petty ◽  
...  

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii403-iii404
Author(s):  
Osama Youssef ◽  
Jeff Turner ◽  
Gongping He ◽  
Jingye Yang ◽  
Samuel Cheshier

Abstract Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor. The Group 3 molecular subgroup of Medulloblastoma (Group 3 MB) is the deadliest with only 30% long term survival. Irradiation for Group 3 Medulloblastoma is required for long term survival of children. Methods to enhance the effect of irradiation against Group 3 MB are an active area of investigation. Immunotherapy using the anti-CD47 treatment has shown promise in treating Group 3 MB. We recently demonstrated that irradiation significantly enhanced anti-CD47-mediated phagocytosis of high-grade glioma cells in vitro. Furthermore, mice engrafted with human high-grade glioma that received anti-CD47 combined with irradiation showed a significant increase in the survival rate and a significant decrease in tumor growth than those that received a single treatment. We have now extended these studies to demonstrate the enhancement of anti-CD47-dependent phagocytosis of human Group 3 MB with irradiation. We also analyzed normal human neural stem cells exposed to the same treatments to assess for the potential toxicity that uniquely exists with this treatment combination.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii472-iii472
Author(s):  
Angela Richardson ◽  
Sara Collins ◽  
Akihito Inagaki ◽  
Valerie Armstrong ◽  
David Robbins ◽  
...  

Abstract Toca 511, a clinical-stage tumor-selective retroviral replicating vector (RRV), encodes optimized yeast cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU) within infected cancer cells. In preclinical models of intracerebral glioblastoma, 5-FU generated locally by Toca 511 (RRV-CD) prodrug activator gene therapy has also been shown to kill immunosuppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. Early-phase clinical trials of Toca 511 in recurrent high-grade glioma showed highly promising evidence of therapeutic benefit, leading to a Phase III trial completed in late 2019 (n=400 patients, randomized 1:1 vs. standard chemotherapy), which appeared to show negative results overall. However, additional analysis showed possible efficacy in prespecified subgroups, and further clinical investigation is being pursued. In preclinical studies, we have also evaluated RRV for use in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Both established and primary human medulloblastoma cell lines supported efficient RRV replication in vitro, with spread to >90% of cells by day 10 post-inoculation, and RRV-CD-transduced medulloblastoma cells showed significant dose-dependent reduction of viability upon exposure to 5-FC, compared to controls. In an intracerebellar HDMB03 medulloblastoma model, RRV-CD-treated mice exhibited long-term survival while on sequential cycles of 5-FC prodrug, until prodrug treatment was stopped, after which 25% long-term survival was observed (median survival 110 days) as compared to controls (median survival 28 days, 100% lethality) (p=0.00007). These results support further evaluation of RRV-mediated prodrug activator gene therapy for pediatric brain tumors.


2021 ◽  
Vol 14 (10) ◽  
pp. e246423
Author(s):  
Jason W Adams ◽  
Denise Malicki ◽  
Michael Levy ◽  
John Ross Crawford

2018 ◽  
Vol 21 ◽  
pp. S25
Author(s):  
L. Sanchez ◽  
P. Lorenzo-Luaces ◽  
C. Viada Gonzalez

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