Imperial College London
Alternate

Professor Amin Hajitou

Faculty of Medicine, Department of Brain Sciences

Professor of Targeted Therapeutics
 
 
 
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Contact

 

+44 (0)20 7594 6546a.hajitou Website

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Al-Bahrani:2023:10.1096/fj.202300045R,
author = {Al-Bahrani, M and Asavarut, P and Waramit, S and Suwan, K and Hajitou, A},
doi = {10.1096/fj.202300045R},
journal = {The FASEB Journal},
pages = {1--16},
title = {Transmorphic phage-guided systemic delivery of TNFα gene for the treatment of human pediatric medulloblastoma},
url = {http://dx.doi.org/10.1096/fj.202300045R},
volume = {37},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Medulloblastoma is the most common childhood brain tumor with an unfavorable prognosis and limited options of harmful treatments that are associated with devastating long-term side effects. Therefore, the development of safe, noninvasive, and effective therapeutic approaches is required to save the quality of life of young medulloblastoma survivors. We postulated that therapeutic targeting is a solution. Thus, we used a recently designed tumor-targeted bacteriophage (phage)-derived particle, named transmorphic phage/AAV, TPA, to deliver a transgene expressing the tumor necrosis factor-alpha (TNFα) for targeted systemic therapy of medulloblastoma. This vector was engineered to display the double-cyclic RGD4C ligand to selectively target tumors after intravenous administration. Furthermore, the lack of native phage tropism in mammalian cells warrants safe and selective systemic delivery to the tumor microenvironment. In vitro RGD4C.TPA.TNFα treatment of human medulloblastoma cells generated efficient and selective TNFα expression, subsequently triggering cell death. Combination with the chemotherapeutic drug cisplatin used clinically against medulloblastoma resulted in augmented effect through the enhancement of TNFα gene expression. Systemic administration of RGD4C.TPA.TNFα to mice-bearing subcutaneous medulloblastoma xenografts resulted in selective tumor homing of these particles and consequently, targeted tumor expression of TNFα, apoptosis, and destruction of the tumor vasculature. Thus, our RGD4C.TPA.TNFα particle provides selective and efficient systemic delivery of TNFα to medulloblastoma, yielding a potential TNFα anti-medulloblastoma therapy while sparing healthy tissues from the systemic toxicity of this cytokine.
AU  - Al-Bahrani,M
AU  - Asavarut,P
AU  - Waramit,S
AU  - Suwan,K
AU  - Hajitou,A
DO  - 10.1096/fj.202300045R
EP  - 16
PY  - 2023///
SN  - 0892-6638
SP  - 1
TI  - Transmorphic phage-guided systemic delivery of TNFα gene for the treatment of human pediatric medulloblastoma
T2  - The FASEB Journal
UR  - http://dx.doi.org/10.1096/fj.202300045R
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37331004
UR  - https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202300045R
UR  - http://hdl.handle.net/10044/1/105215
VL  - 37
ER  -
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