Abstract 133: Micro-environment on demand (MOD): A versatile technology for cognate T-cell receptor - neoantigen discovery

Abstract

Abstract NCI estimates that cancer will be the leading cause of death in 2030, worldwide. Checkpoint inhibitors and adoptive cell therapies (ACTs) cost up to ~$2 million/patient and have shown durable responses in a few patients while many patients experience life-threatening side-effects. So, there is a critical need to identify cost-effective therapies to treat cancer with minimal to no side-effects. Deep mapping of cancer antigens and their cognate immune cells is one approach that has the potential for a more universal/targeted treatment. However, systematic methods do not exist to identify cancer antigens and their cognate immune cells functionally and link phenotypic readouts to antigen and immune cell DNA sequences. Here we present a single cell handling and analysis platform based on Printed Droplet Microfluidics, a new droplet microfluidic technology that enables the precise construction of cell-cell interaction experiments with single cell resolution, followed by functional and genomic analysis. At the core of the technology is a fluorescence-activated flow sorter repurposed to deterministically sort and merge droplets containing single cells, beads, reagents, and drugs, collect and assay merged droplets and resort assay-positive droplets for downstream genomic analyses. The selectivity of the sorting/merging technology enables both the construction of experiments with up to one million precise cell combinations and the performance of flexible multi-step molecular biology workflows. We will show proof-of-concept for the MOD platform that integrates three technologies after fluorescently labeled single-cells are encapsulated in droplets - droplet-based cell-sorting and merging, single-cell-based cytokine assays and selective sequencing of T-cell receptor variable regions based on cytokine signals. The technology has the potential to rapidly accelerate the rate of immunotherapy discovery by enabling a larger number of experiments to be performed with higher precision, more modes of analysis, and less starting material than competing bulk technologies. Citation Format: Maithreyan Srinivasan, Justin Madrigal, Nathan Schoepp, Russell Cole. Micro-environment on demand (MOD): A versatile technology for cognate T-cell receptor - neoantigen discovery [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 133.