Harnessing the Most Powerful Cells Crucial to Accelerating Curative Medicines

Precision Biomarkers for Accelerating & Improving Immune Therapies

Characterizing immune cell function is essential for understanding the relationship between immune cells and cancer cells and improving the therapeutic efficacy of immune-oncology approaches. IsoPlexis has a proven track record^1-4 of helping scientists discover links between immune cell function and therapeutic outcomes. In a 2018 study published in the journal Blood, Rossi et al. used IsoPlexis’ single-cell secretomic analysis to establish a link between polyfunctional chimeric antigen receptor (CAR) T cells in pre-infusion CD19 CAR products and patient responses to treatment.¹

The same platform used in the Blood study was used by researchers Parisi et al. to predict the anti-tumor response of a novel kinetically engineered IL-2 agonist, NKTR-214, with adoptive cell transfer (ACT) compared to the conventional IL-2 combination therapy. IsoPlexis’ platform found that ACT with NKTR-214 resulted in increased proliferation, homing, and persistence of anti-tumor T cells in a murine melanoma model. This resulted in superior anti-tumor activity, and the use of NKTR-214 led to an increase of polyfunctional T cells in murine spleens and tumors. Enhanced polyfunctionality of T and NK cells in the peripheral blood of human patients suggested that NKTR-214 has the potential to improve the anti-tumor effects of ACT in humans. These results highlight critical insights of functional immune profiling for uncovering biomarkers that help predict treatment response.⁵

Identifying Key Prognostic Biomarkers of Inflammation in COVID-19

IsoPlexis’ functional immune landscaping has been used to investigate the mechanism of COVID-19 inflammation within a variety of cell types. In a study recently published in Cell, researchers Su et al. conducted deep functional immune profiling of COVID-19 patients ranging in disease severity compared to healthy samples. They found that with increasing disease severity as measured by the WHO Ordinal Scale (WOS), CD-4⁺ T cell, CD-8⁺ T cell, and NK cell percentages dropped while the proportion of monocytes increased. Su et al. noted a surprising similarity between healthy subjects and mild COVID-19 cases, as well as between moderate and severe cases. IsoPlexis’ functional immune landscaping was able to shed light on the functional mechanisms behind the differences in disease severity.

The severity of COVID-19 correlated with an increase of polyfunctionality in CD8⁺ T cells, followed by a significant drop in function at severe stages of the disease, but “unlike the case of CD8⁺ and CD4⁺ T cells, the [polyfunctional strength index (PSI) of monocytes] monotonically increases with disease severity, suggesting that monocytes contribute to the pro-inflammatory condition of moderate or severe COVID-19.⁶” Researchers Su et al. used IsoPlexis’ uniquely correlative metrics to assess the relationship between highly functional cell subsets and COVID-19 disease progression. Monocytes showed a sharp increase in function between the mild and moderate disease stages, while the monocyte population and PSI continued to increase between moderate and severe cases. These unique findings, enabled by IsoPlexis’ single-cell functional proteomics suggest that monocytes may contribute to the pro-inflammatory environment that is characteristic of moderate and severe COVID-19 cases.

A New Layer of Multiplexed Proteomic Biology: Intracellular Signaling Omics for Hyper-Powered Targeted Therapies

With IsoPlexis’ intracellular signaling omics, researchers can identify functional pathways driving therapeutic resistance and develop combination therapies to combat resistant cell states and resolve tumor heterogeneity. IsoPlexis’ intracellular proteome solutions identify polyfunctional cell subsets to provide a comprehensive picture of altered signal transduction networks in tumors, which allow researchers to identify whether therapies targeting protein signaling networks are effective. In another study published in Nature Communications, Su et al. utilized IsoPlexis’ technology to characterize resistance pathways in mutant melanoma cells. IsoPlexis’ solutions identified two distinct subpopulations of cells which took different paths to drug resistance. IsoPlexis’ intracellular signaling omics provided the insights for researchers to identify combination therapies to combat this resistance that were both effective and low in cytotoxicity.⁷

Highly Multiplexed Automated Proteomics for Identifying Druggable Targets to Treat Cancer Metastasis

In contrast to traditional technologies, IsoPlexis’ high-plex walk-away immunoassays provide researchers the ability to highly multiplex (e.g. 30+ cytokines) and fully automate proteomics for accelerated insights. The CodePlex family of solutions uses ultra-small sample volumes (11 μL per sample), enabling critical applications across research disciplines from cancer immunology to infectious diseases. In a study led by Denis Wirtz at Johns Hopkins University, researchers investigated the role of cytokines in promoting or preventing metastatic cancer cell phenotypes. These researchers used the CodePlex technology to simultaneously measure the concentration of 24 soluble molecules. Both cytokines IL-6 and IL-8 were secreted at high concentrations in a specific ratio, while proteins typically associated with promoting tumor metastasis and progression were not elevated, suggesting that both of these cytokines are responsible for driving the density-dependent cell migration within 3D matrices. Wirtz’s team found a synergistic IL-6 and IL-8 mediated paracrine signaling pathway which may provide a new therapeutic target against metastatic cancer cells.⁸

Sparking the Next Big Breakthrough

The IsoLight system was the first solution to solve numerous instrumentation issues of a typical proteomics workflow by consolidating a multi-faceted and laborious process into one automated, walk-away proteomics system. This system is most often used by pharmaceutical companies and core facilities at leading institutions worldwide due to its high throughput. Now the gold standard of single-cell functional proteomics IsoPlexis is known for is available in three different formats: IsoSpark, IsoLight, and IsoSpark Duo.

The introduction of the IsoSpark, a personalized proteomics system for any laboratory, makes unique functional proteomics accessible to every lab, providing an integrated and flexible solution for accelerating curative medicines. At only 30% of the size of the IsoLight, the IsoSpark’s smaller footprint and lower throughput is perfect for researchers wanting to apply functional immune landscaping, intracellular signaling omics, and high-plex automated immunoassays to their research.

The IsoSpark runs up to four chips simultaneously, and both the IsoLight and the IsoSpark Duo run 8 chips for higher throughput. The IsoSpark Duo is ideal for complete functional immune landscaping with the ability to analyze multiple cell types simultaneously in one run.

A New Era for Discovery Biology

IsoPlexis’ functional proteomics is changing how the world thinks about immune cell characterization, showing how harnessing the most powerful cells is changing immune medicine.

The IsoSpark, the IsoLight, and the IsoSpark Duo, along with functional immune landscaping, intracellular signaling omics, and high-plex automated immunoassays are the latest innovations from IsoPlexis. The IsoSpark, introduced on November 11th, is currently available for pre-order in North America and Europe with shipping planned for January 2021.

Experience the innovation that has unlocked the next generation of personalized medicines with unique functional proteomics. Bring IsoPlexis’ gold standard single-cell functional proteomics technology to your laboratory to accelerate the development of curative medicines.

Discover the new era of functional proteomics at IsoPlexis.com/IsoSpark.

References

1. J. Rossi et al., “Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL,” Blood, 132(8):804-814, 2018.
2. D. Li et al., “Persistent polyfunctional chimeric antigen receptor T cells that target glypican 3 eliminate orthotopic hepatocellular carcinomas in mice,” Gastroenterology, 158(8):2250-2265.e20, 2020.
3. A. Schmidts et al., “Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting multiple myeloma,” Blood Adv, 3(21):3248-3260, 2019.
4. H. Zhu et al., “Metabolic reprograming via deletion of CISH in human iPSC-derived NK cells promotes in vivo persistence and enhances anti-tumor activity,” Cell Stem Cell, 27(2):224-237.e6, 2020.
5. G. Parisi et al., “Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist,” Nat Commun, 11:660, 2020.
6. Y. Su et al., “Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19,” Cell, 2020.
7. Y. Su et al., “Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line,” Nat Commun, 11:2345, 2020.
8. H. Jayatilaka et al., “Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration,” Nat Commun, 8:15584, 2017.