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Functional proteomics is at the forefront of current medical research and has the potential to greatly accelerate therapy development for many complex diseases. IsoPlexis addresses many of the core issues facing researchers by driving the convergence of dynamic proteomics and single-cell biology. IsoPlexis’ multifaceted proteomics provides critical and uniquely capable tools for identifying predictive biomarkers, developing novel curative medicines, and identifying and resolving adaptive resistance pathways. Here, we will highlight two recent studies that used IsoPlexis’ single-cell proteomics and metabolomics to generate predictive insights.
Single-Cell Proteomics Reveals Early Predictive Biomarker of Progression-Free Survival in Metastatic Melanoma
In data presented at the November 2020 SITC conference, IsoPlexis’ single-cell secreted proteomics predicted progression-free survival of metastatic melanoma patients treated with combination Nivo and Bempeg (NKTR-214) therapy. Researchers identified a blood-based biomarker which predicted progression-free survival in melanoma patients after only one week of treatment with Nivo/Bempeg.1 The researchers found that the week 1 Polyfunctional Strength Difference (PSD) of CD8+ T cells, defined as the difference between Polyfunctional Strength Index (PSI) on day 8 and PSI on day 1, predicted progression-free survival in these melanoma patients.1
The predictive blood-based biomarker identified by IsoPlexis’ platform enabled researchers to evaluate patient response to Nivo/Bempeg therapy much earlier than was previously possible with traditional technologies (at week 1). With this finding, IsoPlexis reveals insights into treatment strategies for difficult-to-treat cancers such as metastatic melanomas.
Multi-Omic Energy State: Connecting Functional Signaling Pathways to Energy States for Integrated Cancer Biology
Cancer’s ability to develop resistance to therapy makes treatment challenging. Genomics alone may present challenges in identifying and predicting the development of resistance, as mechanisms of resistance are often due to functional adaptations and not a genomic change. Cells undergo metabolic changes at the beginning of drug adaptation, and because phosphorylated protein signaling plays a vital role in this process, it is critical to analyze single-cell functional phenotypic data on the intracellular proteome in addition to the metabolome.
IsoPlexis’ single-cell pathway omics and metabolomics connect metabolites and functional proteins to the energy states of the cell for the first time, revealing independent trajectories to drug tolerance and enabling new insights for the development of combination therapies to combat and prevent drug resistance. Researchers Su, et al. used the IsoPlexis technology to gain a deeper understanding of the transition from drug responsive to drug tolerant states in BRAFV600E M397 cells, as these cancer cells have demonstrated the ability to quickly become resistant to targeted inhibitors.
After day 1 of BRAF inhibitor (BRAFi) treatment, inhibited glucose intake and suppression of metabolic regulators, signaling phosphoproteins, and Ki67 indicated that the treatment was blocking a key oncogenic signaling pathway. However, a subset of M397 cells was still high in Ki-67, suggesting poorer response to BRAFi.2 Single-cell analysis with IsoPlexis’ technology showed that untreated cells contained MITF-Low and MITF-High cell populations, which took different paths to drug tolerance.2 Using IsoPlexis’ single-cell pathway omics and metabolomics, the researchers were able to identify drug susceptibilities for both pathways, enabling the development of a combination therapy which significantly inhibited tumor growth. With this methodology and IsoPlexis’ unique multi-omic technology, researchers can gain new insights to help inform the development of effective combination therapies and identify highly functional cell subsets which are predictive of patient outcome in complex cancers and beyond.
In the studies described above, IsoPlexis’ technology provided data that correlated with in vivo function and outcome. IsoPlexis is democratizing functional proteomics by addressing the challenges facing researchers such as limited correlation to in vivo biology, limited time, and budget constraints. By providing powerful functional multi-omic solutions for every lab, IsoPlexis is accelerating insights for the development of curative medicines for a range of complex diseases.
1. Diab A, et al. Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study. Presented at: SITC 2020; November 11-14, 2020. Abstract 420. Journal for ImmunoTherapy of Cancer 2020.
2. Su Y, et al. Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line. Nature Communications 2020; 11: 2345.
Download the paper summary: isoplexis.com/met-paper