Checkpoint Therapy Development and Biomarkers: Why Single-Cell Proteomics Is a Powerful Source of Insight

Current Limitations in Predictive Biomarkers

Immune checkpoint inhibitors (CPIs) are proving to be an effective method in treating many different types of cancer. Both pembrolizumab and atezolizumab in combination therapies are approved as a first line of treatment for those with metastatic non-small cell lung cancer (NSCLC). While this is an incredible achievement, there is still a need for predictive biomarkers, as demonstrated by the number of new checkpoint trials started each year in the above chart. Clinical evidence shows that some forms of NSCLC, regardless of PD-L1 expression, do not respond well to CPIs, demonstrating the need for more predictive biomarkers.

Technological Shifts Are Paving the Way for New Predictive Biomarkers: Functional Single-Cell Proteomics

A study was performed using IsoPlexis’ multiplexed proteomics profiling platform to identify a clinically relevant biomarker showing early response to CPI treatment. Because use of the IsoCode Chip does not requre fixing or permeabilizing of cells as with legacy technologies, the true cytokine secretions from live, single T cells can be identified and measured. The ability to obtain this information from live cells means that IsoPlexis’ differentiated system finds correlates that were impossible before, by detecting highly polyfunctional cells, which have correlated to in vivo outcomes.

The Single-Cell Polyfunctional Strength panel on the IsoCode Chip can detect over 32 cytokines per single cell, helping researchers to better understand and functionally characterize their samples. This functional profiling is key in providing insight in the development of checkpoint therapies as well as identifying potential biomarkers.

This study demonstrates the feasibility of using functional proteomics, such as IsoPlexis’ single-cell functional cytokine detection system, to functionally profile cytokines released by live single cells from NSCLC patients. In addition, the data presented PSI as a potential predictive biomarker of CPI response, linking single-cell cytokine profiling to in vivo clinical outcome. The revolutionary system from IsoPlexis is the only one currently able to provide this powerful, needed metric that has correlated in various studies.

IsoPlexis’ Functional Single-Cell Platform as a Standard for Immunotherapy Biomarkers

IsoPlexis’ platform was featured in a chapter of Biomarkers for Immunotherapy of Cancer (Springer 2019). The IsoLight was selected as a uniquely beneficial system for the standardization for biomarkers for immunotherapy of cancer by Springer. IsoPlexis’ IsoLight was one of three tools, and the only cellular functional analysis tool in the book, selected as a biomarker for immunotherapy in cell phenotyping (mass cytometry and highly sensitive bulk ELISA were also selected). This is a testament to the data generated, and our rapidly growing user base, as we continue to demonstrate the standardization of our system for assessing correlative cellular fitness, determining optimal cell therapies in development, and providing advanced immune monitoring in checkpoint therapy and bispecifics. This unique ability provides a powerful solution to unmet needs in immunotherapy profiling. Our chapter, “Single-Cell Multiplexed Proteomics on the IsoLight Resolves Cellular Functional Heterogeneity to Reveal Clinical Responses of Cancer Patients to Immunotherapies” can be found here.

To learn more about how single-cell functional proteomics can change the way you approach therapies, download our eBook, “Single-Cell Functional Proteomics Accelerates Immunotherapy Development: Opportunities from Pre-Clinical to Clinical Stages,” here.

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