Imperial College London
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Professor David W. McComb

Faculty of Engineering, Department of Materials

Adjunct Professor
 
 
 
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Contact

 

+44 (0)20 7594 6750d.mccomb Website

 
 
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Location

 

Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Li:2021:10.1038/s41467-021-27434-x,
author = {Li, W and Zhang, X and Zhang, C and Yan, J and Hou, X and Du, S and Zeng, C and Zhao, W and Deng, B and McComb, DW and Zhang, Y and Kang, DD and Li, J and Carson, WE and Dong, Y},
doi = {10.1038/s41467-021-27434-x},
journal = {Nat Commun},
title = {Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy.},
url = {http://dx.doi.org/10.1038/s41467-021-27434-x},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.
AU  - Li,W
AU  - Zhang,X
AU  - Zhang,C
AU  - Yan,J
AU  - Hou,X
AU  - Du,S
AU  - Zeng,C
AU  - Zhao,W
AU  - Deng,B
AU  - McComb,DW
AU  - Zhang,Y
AU  - Kang,DD
AU  - Li,J
AU  - Carson,WE
AU  - Dong,Y
DO  - 10.1038/s41467-021-27434-x
PY  - 2021///
TI  - Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy.
T2  - Nat Commun
UR  - http://dx.doi.org/10.1038/s41467-021-27434-x
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34907171
VL  - 12
ER  -
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