| First Author | Koch PD | Year | 2020 |
| Journal | Cell Chem Biol | Volume | 27 |
| Issue | 1 | Pages | 94-104.e5 |
| PubMed ID | 31902676 | Mgi Jnum | J:348072 |
| Mgi Id | MGI:7625803 | Doi | 10.1016/j.chembiol.2019.12.007 |
| Citation | Koch PD, et al. (2020) Myeloid Cell-Targeted Nanocarriers Efficiently Inhibit Cellular Inhibitor of Apoptosis for Cancer Immunotherapy. Cell Chem Biol 27(1):94-104.e5 |
| abstractText | 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. |
