Evidence map›Paper›PMID 29702142›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2018

Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.

Rui Kuai, Xiaoqi Sun, Wenmin Yuan, Lukasz J Ochyl, Yao Xu, Alireza Hassani Najafabadi, Lindsay Scheetz, Min-Zhi Yu, Ishina Balwani, Anna Schwendeman and 1 more

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 132 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
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  7. Article
  8. Review
  9. Nanovaccines empowering CD8Theranostics · 2025
    Review
  10. Current Landscape of Therapeutic Cancer Vaccines.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  11. Review
  12. Engineering bioactive mineralized tumor cells for tumor immunotherapy.Frontiers in bioengineering and biotechnology · 2025
    Article
  13. Nanoparticles-Assisted Peptide Cancer Vaccine Delivery.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Rui KuaiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Xiaoqi SunDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Wenmin YuanDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Lukasz J OchylDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Yao XuDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Alireza Hassani NajafabadiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Lindsay ScheetzDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Min-Zhi YuDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Ishina BalwaniDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Anna SchwendemanDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: annaschw@umich.edu.
James J MoonDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: moonjj@umich.edu.
University of Michigan · US

Funding

INTERDEPARTMENTAL TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007767 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ISOM, LORI L. · 1985 to 2019
$10.2M
KLF14 and Cardiovascular DiseaseR01HL134569 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2017 to 2024
$5.3M
Elicitation of mucosal immune responses against HIVR01AI127070 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOON, JAMES J. · 2016 to 2020
$2.3M
Nanomaterials for eliciting anti-tumor T-cells-Diversity SupplementR01CA210273 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOON, JAMES J. · 2017 to 2021
$2.2M
Tuning Biomaterials-immune cell interactions for treatment of glioblastoma multiformeR01EB022563 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOON, JAMES J. · 2016 to 2019
$1.7M
HDL-Loaded Nanoparticles for Glioma TherapeuticsR21NS091555 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2015 to 2016
$427k
NCI NIH HHS R01 CA210273NHLBI NIH HHS R01 HL134569NIAID NIH HHS R01 AI127070NIBIB NIH HHS R01 EB022563NIGMS NIH HHS T32 GM007767NINDS NIH HHS R21 NS091555
6 · The paper itself

Abstract

Recent studies have shown that certain combinations of Toll-like receptor (TLR) agonists can induce synergistic immune activation. However, it remains challenging to achieve such robust responses in vivo in a manner that is effective, facile, and amenable for clinical translation. Here, we show that MPLA, a TLR4 agonist, and CpG, a TLR9 agonist, can be efficiently co-loaded into synthetic high-density lipoprotein nanodiscs, forming a potent adjuvant system (ND-MPLA/CpG) that can be readily combined with a variety of subunit antigens, including proteins and peptides. ND-MPLA/CpG significantly enhanced activation of dendritic cells, compared with free dual adjuvants or nanodiscs delivering a single TLR agonist. Importantly, mice immunized with physical mixtures of protein antigens ND-MPLA/CpG generated strong humoral responses, including induction of IgG responses against protein convertase subtilisin/kexin 9 (PCSK9), leading to 17-30% reduction of the total plasma cholesterol levels. Moreover, ND-MPLA/CpG exerted strong anti-tumor efficacy in multiple murine tumor models. Compared with free adjuvants, ND-MPLA/CpG admixed with ovalbumin markedly improved antigen-specific CD8+ T cell responses by 8-fold and promoted regression of B16F10-OVA melanoma (P < 0.0001). Furthermore, ND-MPLA/CpG admixed with E7 peptide antigen elicited ~20% E7-specific CD8+ T cell responses and achieved complete regression of established TC-1 tumors in all treated animals. Taken together, our work highlights the simplicity, versatility, and potency of dual TLR agonist nanodiscs for applications in vaccines and cancer immunotherapy.

Indexed as

Adjuvants, ImmunologicAnimalsCells, CulturedDrug CarriersFemaleHumansImmunity, HumoralImmunizationImmunotherapyLipid AMelanomaMiceMice, Inbred C57BLNanostructuresOligodeoxyribonucleotidesToll-Like Receptor 4Adjuvants, ImmunologicCPG-oligonucleotideDrug CarriersLipid Amonophosphoryl lipid AOligodeoxyribonucleotidesToll-Like Receptor 4Toll-Like Receptor 9VaccinesAdjuvantCancerImmunotherapyNanoparticleVaccine

Identifiers

PMID29702142
PMCPMC6056764
OpenAlexW2801138628

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.