en
Scientific article
Open access
English

Myeloid cell-targeted nanocarriers efficiently inhibit cellular inhibitor of apoptosis for cancer immunotherapy

Published inCell chemical biology, vol. 27, no. 1, p. 94-104.e5
Publication date2020-01-16
First online date2020-01-02
Abstract

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.

eng
Keywords
  • Cancer
  • Dendritic cells
  • Drug delivery
  • High-content drug screening
  • Immunotherapy
  • Interleukin-12
  • Nanoparticle
  • Alkynes / chemistry
  • Alkynes / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy
  • Dendritic Cells
  • Drug Carriers / chemistry
  • Drug Evaluation, Preclinical
  • Interleukin-12 / biosynthesis
  • Mice
  • Myeloid Cells / drug effects
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Nanoparticles / chemistry
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Thiazoles / chemistry
  • Thiazoles / pharmacology
Affiliation Not a UNIGE publication
Citation (ISO format)
KOCH, Peter D et al. Myeloid cell-targeted nanocarriers efficiently inhibit cellular inhibitor of apoptosis for cancer immunotherapy. In: Cell chemical biology, 2020, vol. 27, n° 1, p. 94–104.e5. doi: 10.1016/j.chembiol.2019.12.007
Main files (2)
Article (Accepted version)
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Article (Published version)
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Identifiers
ISSN of the journal2451-9448
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