Rapid highly multi-plexed immuno-profiling of solid tumors by SpectralEdge imaging

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PROJECT SUMMARY – ABSTRACT The dramatic impact of immune checkpoint inhibitors (ICIs) has focused interest in investigating immune-tumor cell interactions to understand mechanisms of ICI sensitivity and resistance, to identify patients responsive to specific drugs, and to develop new therapies. Multiplexed tissue imaging is a highly promising approach to tumor immunoprofiling: it can assess many cell types and states within the context of preserved tumor architecture and is compatible with pathology workflows. A critical unmet need exists for multiplex technology with the following capabilities: (1) whole-slide imaging; (2) rapid single-pass data collection; (3) sub- cellular imaging resolution; (4) sufficient immunoprofiling depth; (5) bright-field imaging capability; (6) optical and mechanical stability for accurate image tile stitching; (7) availability of core and customizable antibody panel kits for profiling; and (8) compatibility with established image data standards and formats. This RareCyte – Harvard Medical School Phase II proposal describes SpectralEdgeTM, a breakthrough imaging technology that meets these requirements, performing high-resolution high-plex whole-slide imaging of 20 antigens labelled with fluorophore-conjugated antibodies in a single-pass scan of less than 1 hour. The patented SpectralEdge method involves a novel instrument and software as well as highly validated TissuePlexTM antibody panels. SpectralEdge imaging will accelerate discovery of predictive and prognostic biomarkers, enable pharmacodynamics study of immuno-oncology drugs undergoing clinical trials and ultimately provide clinically actionable diagnostic tests. Aim 1 will focus on engineering and production of a robust, production-ready slide scanner and software for rapid high-resolution 20-plex SpectralEdge whole-slide imaging; it will be based on RareCyte’s existing CyteFinder II imaging system. Production of a research-use-only instrument and reagents to ISO13485 standards will enable subsequent deployment in a clinical setting. Compatibility with current and emerging data format and software standards will enable integration with diverse research and clinical workstreams. Aim 2 will test and validate modular antibody panels for immunophenotyping and tumor cell imaging across a range of tumor types. This will yield validated TissuePlex panels having a core set of immunoprofiling antibodies and antibody “modules” for individual tumor types. Aim 3 will test SpectralEdge imaging on well-characterized sample cohorts in: (i) translational biomarker discovery, (ii) industry-sponsored and investigator-initiated immuno-oncology trials, (iii) mouse models of cancer, and (iv) clinical specimens currently undergoing immunoprofiling with other diagnostic methods. Clinical sample studies will be overseen by an advisory group of board-certified HMS pathologists.