Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression

Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Felix Salazar, Bingbing Sun, Wen Jiang, Chong Hyun Chang, Jinhong Jiang, Xiang Wang, Anna M. Wu, Huan Meng () and Andre E. Nel ()
Additional contact information
Jianqin Lu: Department of Medicine, David Geffen School of Medicine, University of California
Xiangsheng Liu: Department of Medicine, David Geffen School of Medicine, University of California
Yu-Pei Liao: Department of Medicine, David Geffen School of Medicine, University of California
Felix Salazar: Department of Molecular and Medical Pharmacology Crump Institute for Molecular Imaging, David Geffen School of Medicine
Bingbing Sun: Department of Medicine, David Geffen School of Medicine, University of California
Wen Jiang: California NanoSystems Institute, University of California
Chong Hyun Chang: California NanoSystems Institute, University of California
Jinhong Jiang: California NanoSystems Institute, University of California
Xiang Wang: California NanoSystems Institute, University of California
Anna M. Wu: Department of Molecular and Medical Pharmacology Crump Institute for Molecular Imaging, David Geffen School of Medicine
Huan Meng: Department of Medicine, David Geffen School of Medicine, University of California
Andre E. Nel: Department of Medicine, David Geffen School of Medicine, University of California

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract While chemotherapy delivery by nanocarriers has modestly improved the survival prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement of the immune response could be game changing. We demonstrate a nano-enabled approach for accomplishing robust anti-PDAC immunity in syngeneic mice through the induction of immunogenic cell death (ICD) as well as interfering in the immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished by conjugating the IDO inhibitor, indoximod (IND), to a phospholipid that allows prodrug self-assembly into nanovesicles or incorporation into a lipid bilayer that encapsulates mesoporous silica nanoparticles (MSNP). The porous MSNP interior allows contemporaneous delivery of the ICD-inducing chemotherapeutic agent, oxaliplatin (OX). The nanovesicles plus free OX or OX/IND-MSNP induce effective innate and adaptive anti-PDAC immunity when used in a vaccination approach, direct tumor injection or intravenous biodistribution to an orthotopic PDAC site. Significant tumor reduction or eradication is accomplishable by recruiting cytotoxic T lymphocytes, concomitant with downregulation of Foxp3+ T cells.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01651-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01651-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01651-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().