Imperial College London
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DrJunIshihara

Faculty of Engineering, Department of Bioengineering

Lecturer
 
 
 
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Contact

 

j.ishihara Website CV

 
 
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Location

 

86 Woodlane London W12 0BZSir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mansurov:2020:10.1038/s41551-020-0549-2,
author = {Mansurov, A and Ishihara, J and Hosseinchi, P and Potin, L and Marchell, TM and Ishihara, A and Williford, J-M and Alpar, AT and Raczy, MM and Gray, LT and Swartz, MA and Hubbell, JA},
doi = {10.1038/s41551-020-0549-2},
journal = {Nature Biomedical Engineering},
pages = {531--543},
title = {Collagen-binding IL-12 enhances tumour inflammation and drives the complete remission of established immunologically cold mouse tumours},
url = {http://dx.doi.org/10.1038/s41551-020-0549-2},
volume = {4},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Checkpoint-inhibitor (CPI) immunotherapy has achieved remarkable clinical success, yet its efficacy in ‘immunologically cold’ tumours has been modest. Interleukin-12 (IL-12) is a powerful cytokine that activates the innate and adaptive arms of the immune system; however, the administration of IL-12 has been associated with immune-related adverse events. Here we show that, after intravenous administration of a collagen-binding domain fused to IL-12 (CBD–IL-12) in mice bearing aggressive mouse tumours, CBD–IL-12 accumulates in the tumour stroma due to exposed collagen in the disordered tumour vasculature. In comparison with the administration of unmodified IL-12, CBD–IL-12 induced sustained intratumoural levels of interferon-γ, substantially reduced its systemic levels as well as organ damage and provided superior anticancer efficacy, eliciting complete regression of CPI-unresponsive breast tumours. Furthermore, CBD–IL-12 potently synergized with CPI to eradicate large established melanomas, induced antigen-specific immunological memory and controlled tumour growth in a genetically engineered mouse model of melanoma. CBD–IL-12 may potentiate CPI immunotherapy for immunologically cold tumours.
AU  - Mansurov,A
AU  - Ishihara,J
AU  - Hosseinchi,P
AU  - Potin,L
AU  - Marchell,TM
AU  - Ishihara,A
AU  - Williford,J-M
AU  - Alpar,AT
AU  - Raczy,MM
AU  - Gray,LT
AU  - Swartz,MA
AU  - Hubbell,JA
DO  - 10.1038/s41551-020-0549-2
EP  - 543
PY  - 2020///
SN  - 2157-846X
SP  - 531
TI  - Collagen-binding IL-12 enhances tumour inflammation and drives the complete remission of established immunologically cold mouse tumours
T2  - Nature Biomedical Engineering
UR  - http://dx.doi.org/10.1038/s41551-020-0549-2
UR  - https://www.nature.com/articles/s41551-020-0549-2
UR  - http://hdl.handle.net/10044/1/83774
VL  - 4
ER  -
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