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 more universal/targeted treatment. However, no methods exist that can identify cancer antigens and their cognate immune cells functionally and link phenotypic readouts to antigen and immune cell DNA sequences, 100k-1M cell combinations at a time. 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 interferon-gamma assays and selective sequencing of T-cell receptor variable regions based on interferon-gamma signals.
Learning Objectives:
1. Importance of linked neoantigen/TCR sequence information
2. Microenvironment on demand technology’s role in screening for adoptive cancer cell therapies (T-cell and CAR-Ts)