A New Bioassay Platform Design for the Discovery of Small Molecules with Anticancer Immunotherapeutic Activity

Mar Drugs. 2020 Nov 29;18(12):604. doi: 10.3390/md18120604.

Abstract

Immunotherapy takes advantage of the immune system to prevent, control, and eliminate neoplastic cells. The research in the field has already led to major breakthroughs to treat cancer. In this work, we describe a platform that integrates in vitro bioassays to test the immune response and direct antitumor effects for the preclinical discovery of anticancer candidates. The platform relies on the use of dendritic cells that are professional antigen-presenting cells (APC) able to activate T cells and trigger a primary adaptive immune response. The experimental procedure is based on two phenotypic assays for the selection of chemical leads by both a panel of nine tumor cell lines and growth factor-dependent immature mouse dendritic cells (D1). The positive hits are then validated by a secondary test on human monocyte-derived dendritic cells (MoDCs). The aim of this approach is the selection of potential immunotherapeutic small molecules from natural extracts or chemical libraries.

Keywords: anticancer; bioassay platform; chemical immunology; dendritic cell; drug discovery; high throughput; immunotherapy; screening guidelines.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biological Assay*
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Drug Discovery*
  • High-Throughput Screening Assays
  • Immunity, Innate / drug effects
  • Immunotherapy*
  • Lymphocyte Activation / drug effects
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phenotype
  • Small Molecule Libraries
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries