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A biomimetic assay platform for the interrogation of antigen-dependent anti-tumor T-cell function

To, Jeremy and Quackenbush, Doug and Rowell, Emily and Li, Lilin and Lo, Frederick and Horman, Shane (2021) A biomimetic assay platform for the interrogation of antigen-dependent anti-tumor T-cell function. Communications biology, 4. p. 56. ISSN 2399-3642

Abstract

Overcoming tumor-mediated immunosuppression and enhancing cytotoxic T-cell activity within the tumor microenvironment are two central goals of immuno-oncology (IO) drug discovery initiatives. However, exploratory assays involving immune components are often plagued by low-throughput and poor clinical relevance. Here we present a novel ultra-high-content assay platform for interrogating T-cell-mediated killing of 3D multicellular tumor spheroids. Employing this assay platform in a chemical genomics screen of 1,800 annotated compounds enabled the identification of novel small molecule perturbagens capable of enhancing cytotoxic CD8+ T-cell activity in an antigen-dependent manner. Specifically, cyclin-dependent kinase (CDK) and bromodomain (BRD) protein inhibitors were shown to significantly augment anti-tumor T-cell function by increasing cytolytic granule and type II interferon expression. The described biotechnology screening platform yields multi-parametric, clinically-relevant data and can be employed kinetically for the discovery of novel IO therapeutic agents.

Item Type: Article
Date Deposited: 10 Feb 2021 00:45
Last Modified: 10 Feb 2021 00:45
URI: https://oak.novartis.com/id/eprint/42122

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