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A New Bioassay Platform Design for the Discovery of Small Molecules with Anticancer Immunotherapeutic Activity
Authors:Carmela Gallo  Giusi Barra  Marisa Saponaro  Emiliano Manzo  Laura Fioretto  Marcello Ziaco  Genoveffa Nuzzo  Giuliana d&#x;Ippolito  Raffaele De Palma  Angelo Fontana
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:chemical immunology  immunotherapy  dendritic cell  screening guidelines  drug discovery  anticancer  high throughput  bioassay platform
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