BioMAP T Cell Autoimmune Panel

Gain Insights on T Cell Responses Prior to Clinical Trials

The T Cell Autoimmune Panel includes BioMAP systems comprised of complex co-cultures of immune and adherent human primary cell types. These cell-based assay systems model adaptive immune cell microenvironment and T and B cell responses in a platform amenable to compound screening. With the BioMAP T Cell Autoimmune Panel, you can obtain quantitative measures of test agent impact on transitional biomarker readouts (proteins, chemokines, cytokines, cell surface receptors and measures of cell health) appropriate for investigations of rheumatoid arthritis, psoriasis, conditions of chronic inflammation, autoimmune disease, and hematological oncology.

Applications for Drug Discovery with Human-centric BioMAP T Cell Autoimmune Panel

  • Benchmark to seven standard-of-care reference drugs
  • Identify translational biomarkers in clinically relevant disease models
  • Gain insights on indication selection and efficacy, as well as early dosing guidance
  • Obtain tissue-specific data within one assay panel, in systems that model the context of stromal tissue, vascular endothelium, and the germinal centers of secondary lymphoid organs

The BioMAP T Cell Autoimmune Panel distinguishes cytotoxicity, antiproliferative, immune inhibitory, inflammatory, and tissue remodeling responses in cell-based, disease-relevant, biological systems. These systems preserve key signaling networks of the T and B-cell adaptive immune response.

Impact of Crisaborole on Biomarkers in Systems Modeling the Adaptive Immune Response

Data plot of BioMAP Platform immune cellular biomarkers in response to anti-inflammatory therapy treatment.
Figure 1. Assessment of the small molecule crisaborole, a phosphodiesterase 4 (PDE-4) inhibitor, in the BioMAP T Cell Autoimmune Panel, identifies concentration-dependent effects on biomarkers representing immunomodulation, inflammation, and tissue remodeling responses.
 
Crisaborole is not cytotoxic at the concentrations tested in this study, near the clinically relevant concentration (Cmax in the range of 125 ng/ml). At 10 μM, it is antiproliferative to human primary B cells and T cells (grey arrows). Of the 51 cytokine, chemokine, cell surface receptor, and cell health measures quantified in the BioMAP T Cell Autoimmune Panel, crisaborole influenced statistically significant changes in 29, including key inflammation-related activities (decreased E-selectin, VCAM-1, MCP-1, sTNFα, MIG, IP-10, IL-8; increased P-selectin), immunomodulatory activities (decreased CD40, sIgG, sIL-10, sIL-17A, CD38, sIL-17F, CD69, sIL-2; modulated sIL-6), and tissue remodeling activities (decreased sTGFβ; increased sVEGF). Tested concentrations of crisaborole are indicated.

Heatmap Visualization to Compare Crisaborole to Standards of Care

Data visualization in a BioMAP Platform heatmap showing human cell biomarker responses to anti-inflammatory and standards of care treatment.
Figure 2. Distinct outcomes of crisaborole treatment, compared to seven standard-of-care drugs, include increased sVEGF in the HDFSAg system modeling responses in stromal tissue, IL-6 in the BT system modeling secondary lymphoid tissue, and E-Selectin in the SAg system modeling vascular endothelium. Heatmap visualization of biomarker changes with modulated biomarkers in orange if protein levels are increased (log10 ratio > 0.1 and p-value < 0.01), blue if protein levels are decreased (log10 ratio < -0.1 and p-value < 0.01), and white if unchanged.

T Cell Autoimmune Panel Service
Service
  • Test agent profiling (chemicals or biologics) in key BioMAP Systems
  • 4 doses in triplicate
Description
  • Annotation Identification and biological intrepretation of relevant BioMAP activities
  • Benchmarking Direct comparison of test agent to seven (7) standard-of-care reference compounds (Cyclosporine A, Everolimus, Ibrutinib, Idelalisib, Infliximab, Prednisolone, Tofacitinib)
Deliverables
  • Study Report BioMAP profile plots, annotation of statistically significant activities with respect to biological significance, a HeatMAP analysis of test and seven (7) immune-cell targeting standard-of-care drugs and a T Cell Analysis Table comparatively scores the test agent against the seven SoC.
  • Data Report Log ratio data tables, 95% significance envelope, table of cytotoxicities, table of active readouts

Available Systems & Readouts

T Cell Autoimmune Panel Service
BioMAP System Name Human Cell Types Disease/Tissue Relevance Translational Biomarker Readouts
SAg Venular endothelial cells, Peripheral blood mononuclear cells Autoimmune Disease, Chronic Inflammation MCP-1, CD38, CD40, E-Selectin, CD69, IL-8, MIG, PBMC cytotoxicity, Proliferation, SRB
BT B cells, Peripheral blood mononuclear cells Allergy, Asthma, Autoimmunity, Oncology B cell Proliferation, PBMC cytotoxicity, Secreted IgG, sIL-17A, sIL-17F, sIL-2, sIL-6, sTNFα
HDFSAg Dermal fibroblasts, Peripheral blood mononuclear cells Autoimmune Disease, Chronic Inflammation, Rheumatoid Arthritis MCP-1, VCAM-1, Collagen I, IP-10, IL-8, MIG, M-CSF, MMP-1, sIL-10, sIL-17A, sIL-17F, sIL-2, sIL-6, SRB, sTGFβ1, sTNFα, sVEGF
/TH2 TH2 blasts, Venular endothelial cells Allergy, Asthma, Oncology MCP-1, Eotaxin-3, VCAM-1, CD38, CD40, E-Selectin, P-Selectin, CD69, uPAR, Collagen IV, IL-8, MIG, PBMC cytotoxicity, sIL-17A, sIL-17F, SRB