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

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.

SUBMITTER: Koch PD

PROVIDER: S-EPMC7422681 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Koch Peter D PD Rodell Christopher B CB Kohler Rainer H RH Pittet Mikael J MJ Weissleder Ralph R

Cell chemical biology 20200102 1

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-molecul ...[more]

PMID: 31902676

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Dataset Information

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

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

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