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

被引：390

作者：

Lu, Jianqin ^{[1
,2
,3
]}

Liu, Xiangsheng ^{[1
,3
]}

Liao, Yu-Pei ^{[1
]}

Salazar, Felix ^{[4
]}

Sun, Bingbing ^{[1
]}

Jiang, Wen ^{[2
]}

Chang, Chong Hyun ^{[2
,3
]}

Jiang, Jinhong ^{[2
]}

Wang, Xiang ^{[2
]}

Wu, Anna M. ^{[4
]}

Meng, Huan ^{[1
,2
,3
,5
]}

Nel, Andre E. ^{[1
,2
,3
,5
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div NanoMed, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Calif NanoSyst Inst, Ctr Environm Implicat Nanotechnol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

MESOPOROUS SILICA NANOPARTICLES; INDOLEAMINE 2,3-DIOXYGENASE; DUCTAL ADENOCARCINOMA; DENDRITIC CELLS; PHASE-I; CHEMOTHERAPY; GEMCITABINE; DELIVERY; PHARMACOKINETICS; EFFICACY;

D O I：

10.1038/s41467-017-01651-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 61 条

[1] Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy [J].

Apetoh, Lionel ;

Ghiringhelli, Francois ;

Tesniere, Antoine ;

Obeid, Michel ;

Ortiz, Carla ;

Criollo, Alfredo ;

Mignot, Gregoire ;

Maiuri, M. Chiara ;

Ullrich, Evelyn ;

Saulnier, Patrick ;

Yang, Huan ;

Amigorena, Sebastian ;

Ryffel, Bernard ;

Barrat, Franck J. ;

Saftig, Paul ;

Levi, Francis ;

Lidereau, Rosette ;

Nogues, Catherine ;

Mira, Jean-Paul ;

Chompret, Agnes ;

Joulin, Virginie ;

Clavel-Chapelon, Francoise ;

Bourhis, Jean ;

Andre, Fabrice ;

Delaloge, Suzette ;

Tursz, Thomas ;

Kroemer, Guido ;

Zitvogel, Laurence .

NATURE MEDICINE, 2007, 13 (09) :1050-1059

[2] CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin [J].

Basu, S ;

Binder, RJ ;

Ramalingam, T ;

Srivastava, PK .

IMMUNITY, 2001, 14 (03) :303-313

[3] Combinatorial strategies for the induction of immunogenic cell death [J].

Bezu, Lucillia ;

Gomes-de-Silva, Ligia C. ;

Dewitte, Heleen ;

Breckpot, Karine ;

Fucikova, Jitka ;

Spisek, Radek ;

Galluzzi, Lorenzo ;

Kepp, Oliver ;

Kroemer, Guido .

FRONTIERS IN IMMUNOLOGY, 2015, 6

[4] A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models [J].

Bhattacharyya, Jayanta ;

Bellucci, Joseph J. ;

Weitzhandler, Isaac ;

McDaniel, Jonathan R. ;

Spasojevic, Ivan ;

Li, Xinghai ;

Lin, Chao-Chieh ;

Chi, Jen-Tsan Ashley ;

Chilkoti, Ashutosh .

NATURE COMMUNICATIONS, 2015, 6

[5] Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity [J].

Broz, Miranda L. ;

Binnewies, Mikhail ;

Boldajipour, Bijan ;

Nelson, Amanda E. ;

Pollack, Joshua L. ;

Erle, David J. ;

Barczak, Andrea ;

Rosenblum, Michael D. ;

Daud, Adil ;

Barber, Diane L. ;

Amigorena, Sebastian ;

van't Veer, Laura J. ;

Sperling, Anne I. ;

Wolf, Denise M. ;

Krummel, Matthew F. .

CANCER CELL, 2014, 26 (05) :638-652

[6] Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death [J].

Casares, N ;

Pequignot, MO ;

Tesniere, A ;

Ghiringhelli, F ;

Roux, S ;

Chaput, N ;

Schmitt, E ;

Hamai, A ;

Hervas-Stubbs, S ;

Obeid, M ;

Coutant, F ;

Métivier, D ;

Pichard, E ;

Aucouturier, P ;

Pierron, G ;

Garrido, C ;

Zitvogel, L ;

Kroemer, G .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (12) :1691-1701

[7] Development of a highly active nanoliposomal irinotecan using a novel intraliposomal stabilization strategy [J].

Drummond, DC ;

Noble, CO ;

Guo, ZX ;

Hong, K ;

Park, JW ;

Kirpotin, DB .

CANCER RESEARCH, 2006, 66 (06) :3271-3277

[8] The three Es of cancer immunoediting [J].

Dunn, GP ;

Old, LJ ;

Schreiber, RD .

ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :329-360

[9] nab-Paclitaxel Potentiates Gemcitabine Activity by Reducing Cytidine Deaminase Levels in a Mouse Model of Pancreatic Cancer [J].

Frese, Kristopher K. ;

Neesse, Albrecht ;

Cook, Natalie ;

Bapiro, Tashinga E. ;

Lolkema, Martijn P. ;

Jodrell, Duncan I. ;

Tuveson, David A. .

CANCER DISCOVERY, 2012, 2 (03) :260-269

[10] Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response [J].

Fucikova, Jitka ;

Kralikova, Petra ;

Fialova, Anna ;

Brtnicky, Tomas ;

Rob, Lukas ;

Bartunkova, Jirina ;

Spisek, Radek .

CANCER RESEARCH, 2011, 71 (14) :4821-4833

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