Myeloid Cell-Targeted Nanocarriers Efficiently Inhibit Cellular Inhibitor of Apoptosis for Cancer Immunotherapy.

Alkynes / chemistry Animals Antineoplastic Agents / chemistry Apoptosis / drug effects Cell Line, Tumor Colonic Neoplasms / metabolism Dendritic Cells Drug Carriers / chemistry Drug Evaluation, Preclinical Immunotherapy Interleukin-12 / biosynthesis Mice Myeloid Cells / drug effects Nanoparticles / chemistry Oligopeptides / chemistry Small Molecule Libraries / chemistry Thiazoles / chemistry
cancer dendritic cells drug delivery high-content drug screening immunotherapy interleukin-12 nanoparticle

Journal

Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030

Informations de publication

Date de publication:
16 01 2020
Historique:
received: 14 06 2019
revised: 02 10 2019
accepted: 12 12 2019
pubmed: 7 1 2020
medline: 16 3 2021
entrez: 7 1 2020
Statut: ppublish

Résumé

Immune-checkpoint blockers can promote sustained clinical responses in a subset of cancer patients. Recent research has shown that a subpopulation of tumor-infiltrating dendritic cells functions as gatekeepers, sensitizing tumors to anti-PD-1 treatment via production of interleukin-12 (IL-12). Hypothesizing that myeloid cell-targeted nanomaterials could be used to deliver small-molecule IL-12 inducers, we performed high-content image-based screening to identify the most efficacious small-molecule compounds. Using one lead candidate, LCL161, we created a myeloid-targeted nanoformulation that induced IL-12 production in intratumoral myeloid cells in vivo, slowed tumor growth as a monotherapy, and had no significant systemic toxicity. These results pave the way for developing combination immunotherapeutics by harnessing IL-12 production for immunostimulation.

Identifiants

DOI: 10.1016/j.chembiol.2019.12.007 PMID: 31902676 PMC: PMC7422681
pubmed: 31902676
pii: S2451-9456(19)30424-6
doi: 10.1016/j.chembiol.2019.12.007
pmc: PMC7422681
mid: NIHMS1612621
pii:
doi:

Substances chimiques

Alkynes 0
Antineoplastic Agents 0
Drug Carriers 0
LCL161 0
N,N'-(2,2'-(hexa-2,4-diyne-1,6-diylbis(oxy))bis(2,3-dihydro-1H-indene-2,1-diyl))bis(1-(2-cyclohexyl-2-(2-(methylamino)propanamido)acetyl)pyrrolidine-2-carboxamide) 0
Oligopeptides 0
Small Molecule Libraries 0
Thiazoles 0
Interleukin-12 187348-17-0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

94-104.e5

Subventions

Organisme : NCI NIH HHS
ID : T32 CA079443
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA206997
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204019
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA240239
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206890
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

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Auteurs

Peter D Koch (PD)

Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.

Christopher B Rodell (CB)

Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.

Rainer H Kohler (RH)

Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.

Mikael J Pittet (MJ)

Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.

Ralph Weissleder (R)

Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. Electronic address: rweissleder@mgh.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures acycliques › Alcynes › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Eucaryotes › Animaux › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Systèmes de délivrance de médicaments › Vecteurs de médicaments › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-12 › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Cellules › Cellules myéloïdes › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Oligopeptides › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Bibliothèques de petites molécules › Myeloid Cell-Targeted Nanocarriers Efficiently...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Thiazoles › Myeloid Cell-Targeted Nanocarriers Efficiently...