Spatial Imaging as a Tool for Discovery of New Candidates to Better Predict Response to Immunotherapies
David Rimm, MD, PhD
Monday, April 25, 2022
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Chapters
Introduction
Why Spatial Biology?
What is Required for Spatial Biology Studies?
Hallmarks of Antibody Validation™
Binary Strategy: Positive & Negative Tissues
Binary Strategy: Knockout Models
Knockout Validation is a Single Data Point
Ranged Expression: High and Low Expressing Tissues
Orthogonal Strategy: Mass Spec vs IHC
Multiple Antibody Strategy: Two Antigen Support
Recombinant Strategy: Family Member Cross-Reactivity
Complementary Strategy: Verification of Modification Specificity
Species Reactivity Testing for PDx and Humanized Mouse Models
Introduction of Dr. David Rimm
David Rimm - Presentation
Disclosure Information
Spatial Imaging as a Tool for Discovery
There are NO continuous quantitative assays in Anatomic Pathology
How assays work; terminology of analytics
Molecular Compartmentalization vs Segmentation
Immunofluorescent Image & Molecular Compartmentalization
Immunofluorescence Segmentation- phenotyping Bright Field Segmentation
AstroPath from Janis Taube and Alex Szalay Improving cell segmentation and phenotyping
Serial sections of 2 random TMA spots in a series of 100 lung cancers
Comparison of Cell-based Segmentation vs Molecular Compartmentalization
The case from measuring tissue
Spatial Imaging as a Tool for Discovery
Chromogenic One-Plex – The PD-L1 IHC assay for Immunotherapy
Moving beyond Chromogenic 1-plex – IF to the Clinic?
ImmunoProfile (IP): Scope and Highlights
IP Overall Workflow
Serially Collected Breast Cancer Cases (2011-2014)
QDAP Low HER2 Assay (aka QHER2-low) Tentative Workflow
Example Case #1 : S19_09851_0
Spatial Imaging as a Tool for Discovery
High-plex Methods for Protein Biomarker Discovery
MultiOmyx (from GE to NeoGenomics to ????)
In-depth tissue profiling using multiplexed immunohistochemical consecutive staining single slide
CyCIF – Peter Sorger Lab - Harvard
Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging
Miltenyi Biotec MACSima and Lunaphore Cormet
High-plex Methods for Protein Biomarker Discovery
MIBI-Multiplex Ion Beam Imaging
Multiplexed ion beam imaging of human breast tumors
Imaging Mass Cytometry (IMC)
histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data
Digital Spatial Profiling
ROI Selection
Summary of Protein High-Plex Methods
When will High-Plex be in a CLIA Lab?
Spatial Imaging as a Tool for Discovery
Potential Markers of Resistance-CD66b in CD45 compartment in NSCLC
High expression of CD95 (APO1/Fas) in macrophages melanoma associated with increase recurrence on ICI therapy
Potential Markers of Response
Summary
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