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{Ishihara:2017:10.1126/scitranslmed.aan0401,
author = {Ishihara, J and Fukunaga, K and Ishihara, A and Larsson, HM and Potin, L and Hosseinchi, P and Galliverti, G and Swartz, MA and Hubbell, JA},
doi = {10.1126/scitranslmed.aan0401},
journal = {Science Translational Medicine},
pages = {1--16},
title = {Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events},
url = {http://dx.doi.org/10.1126/scitranslmed.aan0401},
volume = {9},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)–super-affinity peptide derived from placenta growth factor–2 (PlGF-2123–144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123–144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes. Peritumoral injections of PlGF-2123–144–anti-CTLA4 (cytotoxic T lymphocyte antigen 4) and PlGF-2123–144–anti–PD-L1 (programmed death ligand 1) Abs delayed tumor growth and prolonged survival compared to the unmodified Abs in genetically engineered murine tumor models of melanoma and breast cancer. The PlGF-2123–144–Abs increased tumor-infiltrating activated CD8+ and CD4+ T cells, resulting in a delay of distant tumor growth as well. This simple and translatable approach of engineered ECM-binding Abs may present a viable and safer approach in checkpoint blockade.
AU  - Ishihara,J
AU  - Fukunaga,K
AU  - Ishihara,A
AU  - Larsson,HM
AU  - Potin,L
AU  - Hosseinchi,P
AU  - Galliverti,G
AU  - Swartz,MA
AU  - Hubbell,JA
DO  - 10.1126/scitranslmed.aan0401
EP  - 16
PY  - 2017///
SN  - 1946-6234
SP  - 1
TI  - Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events
T2  - Science Translational Medicine
UR  - http://dx.doi.org/10.1126/scitranslmed.aan0401
UR  - https://stm.sciencemag.org/content/9/415/eaan0401
UR  - http://hdl.handle.net/10044/1/83776
VL  - 9
ER  -
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