Each cell has a phenome & is an independent functioning life.
The phenome is the sum of many functions, or collective life, for each cell.
The evolution of functional biology began with immune surface breakthroughs and the advent of flow cytometry, which defined CD4 T cells and enhanced the ability to combat infectious diseases. Following this, significant genome breakthroughs led to the ability to change T cell receptors and create novel therapies such as CAR-T. The era of phenome is now upon us as we increase our scope of biological understanding, enabling the engineering of new therapies with optimal functional phenomes.
In particular, today's solutions typically look at three things:
Our technologies uniquely capture aspects of the phenome required to accelerate biological solutions for thousands of labs in this next era of the phenome.
The Bruker Cellular Analysis Suite of discovery to clinical research technologies can capture the phenome, the collective sum of the parts of the cells, the phenotype, and the functional phenotype, and leverage that to pick the best whole cells and pick the best patient response.
Bruker Cellular Analysis uniquely reveals Potent and Dysfunctional Cells — highly polyfunctional cells that are early actors and orchestrators in the immune response. These rare subsets of highly functional cells can be beneficial (Potent Cells) or detrimental (Dysfunctional Cells). Detecting these cells is critical for developing more effective immune therapies and vaccines.
Potent cells are rare subsets of highly-polyfunctional cells that orchestrate the response against tumors and correlate to potency, persistence, and survival.
Dysfunctional cells are highly-polyfunctional cells that drive disease progression and correlate to inflammation, toxicity, and resistance.
The proteome is complex and requires direct detection. Dynamic in vivo biology is the captured by the proteome— the key to advancing medicines and diagnostics.
Bruker Cellular Analysis technology can uniquely reveal highly functional cells — the 5-10% of cells that are early actors of an immune response. We achieve this by detecting each cell's highly multiplexing cytokines, chemokines, and phosphoproteins.
The IsoSpark's leap in innovation allows researchers to immediately detect the most potent immune cells and leverage that response data for preclinical and translational/clinical research.
The Beacon's breakthrough single-cell functional phenotyping tells you exactly which immune/production cell functionally produces key antibodies/proteins and the receptor/clone data, with the ability to retrieve that live cell.
This leap in innovation allows researchers to immediately detect the most potent cell and leverage it for discovery and bioprocessing.
Cytokine function dictates the response of each cell to the tumor:
With the leaders from Kite Pharma and NCI: in a 20-patient non-Hodgkin Lymphoma CAR-T study, the frequency of highly functional cells (~20-25%), i.e., High PSI of each CAR-T cell therapy product, predicted response - Flow Cytometry & Bulk ELISA did not. Functional single-cell biology uniquely provides this information and can be targeted to create better products before release.
Emergency Use Authorization of AstraZeneca’s Evuseld: Researchers at Vanderbilt used our Optofluidic platform to discover the antibodies from primary human tissues. Patients given a single injection of the antibody treatment were 83% less likely to develop symptomatic cases of the coronavirus than participants who were given a placebo.
In a separate trial, patients with mild-to-moderate COVID-19 who were given one dose of antibody treatment within three days of developing symptoms had a reduced risk of developing severe disease by 88%.
Results published in Nature Medicine.
Every B cell can produce a unique antibody, and discovering the most potent antibody often requires finding the rate B cell in a highly diverse cell population.
Antibody discovery using the traditional hybridoma approach requires the immortalization of B cells by cell fusion that results in the death of >90% of B cells. This significantly reduces the chances of discovering novel antibodies against difficult targets.
Opto B Discovery workflows on the Beacon systems increase the probability of finding the best antibody by direct functional assessment of antibody products by single B cells.
Our proprietary & patented “Proteomic Barcoded” IsoCode Chip, named the Scientist's number #1 innovation, works by detecting 30+ cytokines per cell, measuring the functional phenotype of each immune cell.
This breakthrough technical innovation allows for complete single-cell functional characterization — something that was not possible before.
Our OEP fluidics uses light and millions of light-actuated pixels to move individual cells to be isolated, cultured, assayed, and exported. Each cell or clone is imaged and monitored in real-time in a NanoPen™ chamber on our OptoSelect™ chips to provide rich visual data early and often. Our Optofluidic product suite delivers cell processing and deep profiling with more information about cell function than any other technology.
Unlike Bruker Cellular Analysis, these traditional methods are unable to detect the functional biological drivers that can lead to biomarker breakthroughs.
Our technology addresses the core problem that immune cells, which play a major role in cancer immunology, are heterogenous.
Bruker Cellular Analysis enables researchers to fine-tune their immunotherapeutic candidates and identify what differentiates immune cell potency, cell product toxicity, and functional differences between patient responders and non-responders to immunotherapies.
IsoSpeak is the first automated informatics suite for advanced, functional, single-cell mapping and visualizations which can reveal correlative insights into true, functional immune biology.
Researchers use IsoSpeak to make sense of complex single-cell data by generating meaningful visualizations with the click of a button.
IsoSpeak's push-button user interface and advanced automation allows users to visualize, target, and utilize data from direct, functional cytokine profiling of single cells.
Researchers can use IsoSpeak to automatically generate a unique set of cellular visualizations, sample annotations, and report-ready single-cell readouts.
The Dominant Functional Group mapping displays a color-coded visualization of data points based on the cytokine profile being secreted. These include inflammatory, regulatory, chemoattractive, stimulatory, and effector cytokine profiles. Non-secretors are displayed in grey.
Bruker Cellular Analysis' t-SNE functional graphs plot cells by differentiating them based on their greatest cytokine-based functional differences.
IsoSpeak can visualize stratification differences driving responders vs. non-responders as shown in 40+ precedent data sets.
Visualized within the same functional plot, the t-SNE graph uncovers functional sources of the cellular biomarkers of response.
Multi-functional cells (also termed polyfunctional cells) secreting multiple cytokines are upregulated in responders.
IsoSpeak reveals functional biological drivers in the various cytokines.
Click to explore 3D visualization types:
Bruker Cellular Analysis' functional phenotyping is critical to finding what's really happening in patients — as shown in 40+ correlative cancer immunology cases. Our functional phenotypes are illustrating the large patient differences between different types of patient responses that are undetectable on other platforms.
Bruker Cellular Analysis' functional phenotyping has been published and presented by leaders in various clinical and preclinical studies.
Additionally, we've translated that insight to accelerate pre-clinical development — illustrating large differences leading to choice.
|Potency||CAR-T||Preclinical Discovery||Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice||JCI Insight , 2021||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|CAR-T||Preclinical Discovery||4-1BB and optimized CD28 co-stimulation enhances function of human mono-specific and bi-specific third-generation CAR T cells||Journal for Immunotherapy of Cancer, 2021||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|T-Cells||Clinical Biomarker||Single-cell polyfunctional proteomics of CD4 cells from patients with AML predicts responses to anti-PD-1-based therapy||Blood Advances, 2021||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|Potency||TILs||Manufacturing & Product QC, Clinical Biomarker||Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial||Nature Medicine, 2021||IsoCode Single-Cell Adaptive Immune: Human T-Cell|
|Potency||CAR-T||Manufacturing & Product QC, Clinical Biomarker||CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial||Nature Medicine, 2021||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|Efficacy||NK Cells||Preclinical Discovery||Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation||Communications Biology, 2021||IsoCode Single-Cell Adaptive Immune: Human NK Cell|
|T-Cells||Preclinical Discovery, Clinical Biomarker||Venetoclax enhances T cell-mediated antileukemic activity by increasing ROS production||Blood, 2021||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|T-Cells||Clinical Biomarker||Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma||Journal of Clinical Oncology, 2021||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|Potency||NK Cells||Preclinical Discovery||Transient blockade of TBK1/IKKε allows efficient transduction of primary human natural killer cells with vesicular stomatitis virus G-pseudotyped lentiviral vectors||Cytotherapy, 2021||IsoCode Single-Cell Adaptive Immune: Human NK Cell|
|Potency||NK Cells||Preclinical Discovery||NF-κB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells||Frontiers in Immunology, 2021||IsoCode Single-Cell Adaptive Immune: Human NK Cell|
|Potency||CAR-T||Preclinical Discovery||Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity||Molecular Therapy, 2021||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|Potency||T-Cells||Preclinical Discovery, Clinical Biomarker||Use of Multi-Site Radiation Therapy for Systemic Disease Control||International Journal of Radiation Oncology, Biology, Physics, 2021||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|Response||T-Cells||Clinical Biomarker||Changes in peripheral and local tumor immunity after neoadjuvant chemotherapy reshape clinical outcomes in patients with breast cancer||Clinical Cancer Research, 2020||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|Potency||T-Cells||Preclinical Discovery||Targeted Co-delivery of Tumor Antigen and α-Galactosylceramide to CD141+ Dendritic Cells Induces a Potent Tumor Antigen-Specific Human CD8+ T Cell Response in Human Immune System Mice||Frontiers in Immunology, 2020||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|NK Cells||Preclinical Discovery||Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes in vivo Persistence and Enhances Anti-tumor Activity||Cell Stem Cell, 2020||IsoCode Single-Cell Adaptive Immune: Human NK Cell|
|Potency||CAR-T||Preclinical Discovery||CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression||Leukemia, 2020||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|CAR-T||Preclinical Discovery||Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice||Gastroenterology, 2020||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|T-Cells, NK Cells||Preclinical Discovery, Clinical Biomarker||Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist||Nature Communications, 2020||IsoCode Single-Cell Adaptive Immune: Human PBMC|
|Potency||CAR-T||Preclinical Discovery||Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma||Blood Advances, 2019||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|Response||CAR-T||Clinical Biomarker, Manufacturing & Product QC||Preinfusion Polyfunctional Anti-CD19 Chimeric Antigen Receptor T Cells Associate with Clinical Outcomes in NHL||Blood, 2018||IsoCode Single-Cell Adaptive Immune: Human CAR-T Using AF647-Conjugated Antibodies to CD4 and CD8|
|Potency||T-Cells||Preclinical Discovery, Clinical Biomarker||A Kinetic Investigation of Interacting, Stimulated T Cells Identifies Conditions for Rapid Functional Enhancement, Minimal Phenotype Differentiation, and Improved Adoptive Cell Transfer Tumor Eradication||PLOS One, 2018||IsoCode Single-Cell Adaptive Immune: Human PBMC with PMA & Ionomycin|
Li L et al., "In-depth analysis of SARS-CoV-2-specific T cells reveals diverse differentiation hierarchies in vaccinated individuals", JCI Insight, 2022
Fernandez-Yague MA et al., "Analyzing immune response to engineered hydrogels by hierarchical clustering of inflammatory cell subsets", Science Advances, 2022
Friedman et al., "Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses", Journal for ImmunoTherapy of Cancer, 2022
Su Yet al., "Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae", Cell, 2022
Thomas A et al., "Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice", JCI Insight, 2021
Roselli E et al., "4-1BB and optimized CD28 co-stimulation enhances function of human mono-specific and bi-specific third-generation CAR T cells", Journal for ImmunoTherapy of Cancer, 2021
Abbas H et al., "Single-cell Polyfunctional Proteomics of CD4 Cells from Patients with AML Predicts Responses to Anti-PD-1-based therapy", Blood Advances, 2021
Gionet-Gonzales M et al., "Sulfated Alginate Hydrogels Prolong the Therapeutic Potential of MSC Spheroids by Sequestering the Secretome", Advanced Healthcare Materials, 2021
Creelan BC et al., "Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial", Nature Medicine, 2021
Spiegel JY et al., "CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase I trial", Nature Medicine, 2021
Dhar P et al., "Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation", Communications Biology, 2021
Dhar P et al., "Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation", Communications Biology, 2021
Boklee J et al., "Venetoclax enhances T cell-mediated antileukemic activity by increasing ROS production", Blood, 2021
Diab A et al., "Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma", Journal of Clinical Oncology, 2021
Chockley P et al., "Transient blockade of TBK1/IKKε allows efficient transduction of primary human natural killer cells with vesicular stomatitis virus G-pseudotyped lentiviral vectors", Cytotherapy, 2021
Mahmoud A et al., "Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression", iScience, 2021
Ruiz F et al., "Comprehensive Activation Profiling of Tabelecleucel, an Off-The-Shelf, Allogeneic EBV-Specific T-Cell Immunotherapy", Hematological Oncology, 2021
Vicioso Y et al., "NF-κB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells", Frontiers in Immunology, 2021
Szabo PA et al., "Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19", Immunity, 2021
McKenna MK et al., "Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity", Molecular Therapy, 2021
Patel RR et al., "Use of Multi-Site Radiation Therapy for Systemic Disease Control", International Journal of Radiation Oncology*Biology*Physics. 2021., 2021
Xie CB et al., "Complement‐activated human endothelial cells stimulate increased polyfunctionality in alloreactive T cells", American Journal of Transplantation, 2021
We help researchers around the world accelerate the next generation of cancer immunotherapy with functional immunology.
Gain deeper access to in vivo biology through highly-multiplexed functional cell biology.
Instantly analyze, dissect, visualize, and export your data with a click of a button — no coding required.
Fully automate your workflow with our all-in-one, intuitive system that fits on your lab bench.
Our functional biology can accurately detect what individual T-cells are secreting for the first time, rather than estimations. These unique cellular subsets are depicted as the blue highly polyfunctional cells (cells that secrete two or more cytokines) in the top right of the graph.
Samples with multiple subsets of these cells have high polyfunctional strength, which has correlated with outcome.
The ability to capture the range of relevant cytokines from each immune cell represents a unique secreted protein multiplexing capability. The mechanism for both clinical effects and cytotoxicity can be heavily mediated by cytokines (functional proteins through which immune cells send and receive signals).
Polyfunctional Activation Topology Principal Component Analysis (PAT-PCA) is a high dimensional map showing which cells secrete multiple cytokines per cell and groups them into corresponding functional groups.
The Dominant subgroups will emerge in the PAT-PCA graphs, representing significant multi-functional subsets driving the overall response.
Samples with a higher response dominate the graph. Differences between donors are highlighted through the location of their polyfunctional subsets in the graph.
A polyfunctional heat map is a visualization comparing the frequency at which various functional and polyfunctional groups are secreted by the sample. Use Heterogeneity Heat Maps to uncover the critical cell subpopulations that exist only in the condition/group of interest.
The Single Cell Polyfunctional Strength Index (PSI) aggregates all single-cell, multi-dimensional secretions from a sample into a single index. The readout combines the polyfunctionality of a sample (frequency of cells secreting multiple cytokines) with the signal intensities for each single-cell across the secreted cytokines of the sample. The displayed index is color-coded to show the contribution from different categories of cytokines (e.g., effector vs. stimulatory cytokines).
PSI is the most novel and revealing metric for measuring the potency of different immune cell types, helping top researchers accelerate their immunotherapy programs from discovery to predicting response.