Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

Immunohistochemistry has long been held as the gold standard for understanding the expression patterns of therapeutically relevant proteins to identify prognostic and predictive biomarkers. Patient selection for targeted therapy in oncology has successfully relied upon standard microscopy-based meth...

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Main Authors: Darren Locke, Clifford C. Hoyt
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1051491/full
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author Darren Locke
Clifford C. Hoyt
author_facet Darren Locke
Clifford C. Hoyt
author_sort Darren Locke
collection DOAJ
description Immunohistochemistry has long been held as the gold standard for understanding the expression patterns of therapeutically relevant proteins to identify prognostic and predictive biomarkers. Patient selection for targeted therapy in oncology has successfully relied upon standard microscopy-based methodologies, such as single-marker brightfield chromogenic immunohistochemistry. As promising as these results are, the analysis of one protein, with few exceptions, no longer provides enough information to draw effective conclusions about the probability of treatment response. More multifaceted scientific queries have driven the development of high-throughput and high-order technologies to interrogate biomarker expression patterns and spatial interactions between cell phenotypes in the tumor microenvironment. Such multi-parameter data analysis has been historically reserved for technologies that lack the spatial context that is provided by immunohistochemistry. Over the past decade, technical developments in multiplex fluorescence immunohistochemistry and discoveries made with improving image data analysis platforms have highlighted the importance of spatial relationships between certain biomarkers in understanding a patient’s likelihood to respond to, typically, immune checkpoint inhibitors. At the same time, personalized medicine has instigated changes in both clinical trial design and its conduct in a push to make drug development and cancer treatment more efficient, precise, and economical. Precision medicine in immuno-oncology is being steered by data-driven approaches to gain insight into the tumor and its dynamic interaction with the immune system. This is particularly necessary given the rapid growth in the number of trials involving more than one immune checkpoint drug, and/or using those in combination with conventional cancer treatments. As multiplex methods, like immunofluorescence, push the boundaries of immunohistochemistry, it becomes critical to understand the foundation of this technology and how it can be deployed for use as a regulated test to identify the prospect of response from mono- and combination therapies. To that end, this work will focus on: 1) the scientific, clinical, and economic requirements for developing clinical multiplex immunofluorescence assays; 2) the attributes of the Akoya Phenoptics workflow to support predictive tests, including design principles, verification, and validation needs; 3) regulatory, safety and quality considerations; 4) application of multiplex immunohistochemistry through lab-developed-tests and regulated in vitro diagnostic devices.
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spelling doaj.art-ef00cf64264048a687d0d7810a6db39f2023-02-09T12:17:19ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-02-011010.3389/fmolb.2023.10514911051491Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imagingDarren Locke0Clifford C. Hoyt1Clinical Assay Development, Akoya Biosciences, Marlborough, MA, United StatesTranslational and Scientific Affairs, Akoya Biosciences, Marlborough, MA, United StatesImmunohistochemistry has long been held as the gold standard for understanding the expression patterns of therapeutically relevant proteins to identify prognostic and predictive biomarkers. Patient selection for targeted therapy in oncology has successfully relied upon standard microscopy-based methodologies, such as single-marker brightfield chromogenic immunohistochemistry. As promising as these results are, the analysis of one protein, with few exceptions, no longer provides enough information to draw effective conclusions about the probability of treatment response. More multifaceted scientific queries have driven the development of high-throughput and high-order technologies to interrogate biomarker expression patterns and spatial interactions between cell phenotypes in the tumor microenvironment. Such multi-parameter data analysis has been historically reserved for technologies that lack the spatial context that is provided by immunohistochemistry. Over the past decade, technical developments in multiplex fluorescence immunohistochemistry and discoveries made with improving image data analysis platforms have highlighted the importance of spatial relationships between certain biomarkers in understanding a patient’s likelihood to respond to, typically, immune checkpoint inhibitors. At the same time, personalized medicine has instigated changes in both clinical trial design and its conduct in a push to make drug development and cancer treatment more efficient, precise, and economical. Precision medicine in immuno-oncology is being steered by data-driven approaches to gain insight into the tumor and its dynamic interaction with the immune system. This is particularly necessary given the rapid growth in the number of trials involving more than one immune checkpoint drug, and/or using those in combination with conventional cancer treatments. As multiplex methods, like immunofluorescence, push the boundaries of immunohistochemistry, it becomes critical to understand the foundation of this technology and how it can be deployed for use as a regulated test to identify the prospect of response from mono- and combination therapies. To that end, this work will focus on: 1) the scientific, clinical, and economic requirements for developing clinical multiplex immunofluorescence assays; 2) the attributes of the Akoya Phenoptics workflow to support predictive tests, including design principles, verification, and validation needs; 3) regulatory, safety and quality considerations; 4) application of multiplex immunohistochemistry through lab-developed-tests and regulated in vitro diagnostic devices.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1051491/fullpredictive biomarkerimmuno-oncologycell phenotypingphenopticsmultiplex immunofluorescenceclinical workflow
spellingShingle Darren Locke
Clifford C. Hoyt
Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
Frontiers in Molecular Biosciences
predictive biomarker
immuno-oncology
cell phenotyping
phenoptics
multiplex immunofluorescence
clinical workflow
title Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
title_full Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
title_fullStr Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
title_full_unstemmed Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
title_short Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
title_sort companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging
topic predictive biomarker
immuno-oncology
cell phenotyping
phenoptics
multiplex immunofluorescence
clinical workflow
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1051491/full
work_keys_str_mv AT darrenlocke companiondiagnosticrequirementsforspatialbiologyusingmultipleximmunofluorescenceandmultispectralimaging
AT cliffordchoyt companiondiagnosticrequirementsforspatialbiologyusingmultipleximmunofluorescenceandmultispectralimaging