Journal article
Myeloid Cell-Targeted Nanocarriers Efficiently Inhibit Cellular Inhibitor of Apoptosis for Cancer Immunotherapy
Cell chemical biology, v 27(1), pp 94-104
16 Jan 2020
PMID: 31902676
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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•LCL161 activates IL-12 production in murine dendritic cells•LCL161 can be complexed to nanoparticles for delivery to the tumor microenvironment•LCL161 nanoparticles regress tumors and outperform a free drug control
Koch et al. describe the development of LCL161 nanoparticles for cancer immunotherapy. These nanoparticles deliver the small-molecule drug LCL161 to intratumoral dendritic cells, where it stimulates production of IL-12. This therapeutic could greatly enhance the efficacy of current checkpoint inhibitors.
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Details
- Title
- Myeloid Cell-Targeted Nanocarriers Efficiently Inhibit Cellular Inhibitor of Apoptosis for Cancer Immunotherapy
- Creators
- Peter D. Koch - Center for Systems BiologyChristopher B. Rodell - Center for Systems BiologyRainer H. Kohler - Center for Systems BiologyMikael J. Pittet - Center for Systems BiologyRalph Weissleder - Harvard University
- Publication Details
- Cell chemical biology, v 27(1), pp 94-104
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000507961800012
- Scopus ID
- 2-s2.0-85077662467
- Other Identifier
- 991019168337104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology