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BioMAP® Combo ELECT Combination Study Service

Finding the best drug partners and setting the stage for success in vivo

With potential combination partners to choose from growing exponentially, there is a major need for guidance in designing rational combinations including which agents and what concentrations to use for appropriate in vivo exposures. Target-agnostic based approaches such as in vitro phenotypic assays provide a compelling strategy to compare combinations with the corresponding individual agents in a head-to-head screening format. Testing the efficacy and safety of drugs versus combinations prior to clinical administration can improve the availability and feasibility of such a therapeutic approach.

Applications for Drug Discovery with Combo ELECT

  • Find drug combinations with novel, additive or antagonistic effects
  • Rescue ‘at risk’ compounds due to lack of efficacy or negative early clinical trial results
  • Expand the therapeutic utility of existing clinical drugs and drugs in development
  • Anticipate potential adverse events due to drug combinations for smarter clinical trial design

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Measuring Differential Activity in Drug Combination Studies

Efficacy: Dabrafenib & Trametinib in Combination

       

Identify Unexpected Activities With Potential for Adverse Effects
 
BioMAP profiles for Dabrafenib (red), Trametinib (blue) alone and in combination (black) are shown for one system. The horizontal axis lists the protein biomarkers measured and the vertical axis shows the change in biomarker expression (log ratio) in response to the drugs. The light gray horizontal band shows the range outside of which a change in expression is statistically significant. The combination profile reveals reduced inflammatory activities (noted in red). Additionally, a reduction in tumor cell marker CEACAM5 is observed only in the presence of both drugs. [click graph to enlarge].
  
BioMAP profiles are shown for three systems, each a different combination of human primary cells and activating factors. The horizontal axis lists the protein biomarkers measured and the vertical axis shows the change in biomarker expression (log ratio) in response to the drugs. The light gray horizontal band shows the range outside of which a change in expression is statistically significant. The HPNo system profile shows that the combination of Drug A and Drug B together induces unexpected activities in the BioMAP system relative to either of the single agents alone, suggesting an additive effect [click graph to enlarge]

Combo ELECT Experimental Design

Combination Study Matrix
A 4x4 combination array is created to test all mixtures of two serially diluted single test agents/drugs. Test agents/drugs are screened at 4 concentrations each (3-fold dilutions), in triplicate, in selected BioMAP Systems (50+ human biology and disease model systems available through BioMAP Combo ELECT).
 
Combo ELECT Combination Study Service
Service
  • Compound profiling of two agents in a combination array against selected BioMAP Systems
  • 4 concentrations (3-fold dilutions) in triplicate
Description
  • Annotation Activity annotation and biological relevance of BioMAP activities
Deliverables
  • Study Report BioMAP profile plots, annotation of activities with respect to biological significance, expert data interpretation, graphical overlays of combinations showing significant differential effects
  • Data Report Log ratio data tables, table of cytotoxicities, table of active readouts, table of significant differential activities

Available Systems & Readouts

System ▲RelevanceCell TypeBiomarker Readout
/3CCardiovascular Disease, Chronic InflammationVenular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD54/ICAM-1, CD62E/E-Selectin, CD87/uPAR, CXCL8/IL-8, CXCL9/MIG, HLA-DR, Proliferation, SRB
/4HAllergy, Asthma, OncologyVenular endothelial cellsCCL2/MCP-1, CCL26/Eotaxin-3, CD106/VCAM-1, CD62P/P-Selectin, CD87/uPAR, SRB, VEGFR2
/HDF3CTChronic Inflammation, FibrosisDermal fibroblastsCCL2/MCP-1, CD106/VCAM-1, CD54/ICAM-1, Collagen I, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, M-CSF, MMP-1, PAI-I, SRB, TIMP-2
/HDFTChronic Inflammation, FibrosisDermal fibroblastsCollagen I, Collagen III, PAI-I, SRB, TIMP-1, TIMP-2
/HPNoImmune Biology, Vascular BiologyPeripheral blood mononuclear cells + Venular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD38, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, CXCL9/MIG, M-CSF, sPGE2, SRB, sTNF-α
/LPSCardiovascular Disease, Chronic InflammationPeripheral blood mononuclear cells + Venular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, IL-1 α, M-CSF, sPGE2, SRB, sTNF-α
/MphgCardiovascular Disease, Chronic Inflammation, RestenosisMacrophages + Venular endothelial cellsCCL2/MCP-1, CCL3/MIP-1 α, CD106/VCAM-1, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, IL-1 α, M-CSF, sIL-10, SRB, SRB-Mphg
/MphgNoImmune Biology, Vascular BiologyMacrophages + Venular endothelial cellsCCL2/MCP-1, CCL3/MIP-1 α, CD106/VCAM-1, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, IL-1 α, M-CSF, SRB, SRB-Mphg
/SAgAutoimmune Disease, Chronic InflammationPeripheral blood mononuclear cells + Venular endothelial cellsCCL2/MCP-1, CD38, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, CXCL9/MIG, PBMC Cytotoxicity, Proliferation, SRB
/TH2Allergy, Asthma, OncologyTH2 blasts + Venular endothelial cellsCCL2/MCP-1, CCL26/Eotaxin-3, CD106/VCAM-1, CD38, CD40, CD62E/E-Selectin, CD62P/P-Selectin, CD69, CD87/uPAR, Collagen IV, CXCL8/IL-8, CXCL9/MIG, PBMC Cytotoxicity, sIL-17A, sIL-17F, SRB
/TH2NoTH2 BiologyTH2 blasts + Venular endothelial cellsCCL2/MCP-1, CCL26/Eotaxin-3, CD106/VCAM-1, CD38, CD40, CD62E/E-Selectin, CD62P/P-Selectin, CD69, CD87/uPAR, Collagen IV, CXCL8/IL-8, CXCL9/MIG, PBMC Cytotoxicity, sIL-17A, sIL-17F, SRB
3CCardiovascular Disease, Chronic InflammationVenular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD54/ICAM-1, CD62E/E-Selectin, CD87/uPAR, CXCL8/IL-8, CXCL9/MIG, HLA-DR, Proliferation, SRB
4HAllergy, Asthma, AutoimmunityVenular endothelial cellsCCL2/MCP-1, CCL26/Eotaxin-3, CD106/VCAM-1, CD62P/P-Selectin, CD87/uPAR, SRB, VEGFR2
BE3CCOPD, Lung InflammationBronchial epithelial cellsCD54/ICAM-1, CD87/uPAR, CXCL10/IP-10, CXCL11/I-TAC, CXCL8/IL-8, CXCL9/MIG, EGFR, HLA-DR, IL-1 α, Keratin 8/18, MMP-1, MMP-9, PAI-I, SRB, tPA, uPA
BENoEpithelial Biology, Lung BiologyBronchial epithelial cellsCCL26/Eotaxin-3, CD54/ICAM-1, CD87/uPAR, CXCL10/IP-10, CXCL11/I-TAC, CXCL8/IL-8, CXCL9/MIG, EGFR, HLA-DR, IL-1 α, Keratin 8/18, MMP-1, MMP-9, PAI-I, SRB, tPA, uPA
BF4TAllergy, Asthma, Fibrosis, Lung InflammationBronchial epithelial cells + Dermal fibroblastsCCL2/MCP-1, CCL26/Eotaxin-3, CD106/VCAM-1, CD54/ICAM-1, CD90, CXCL8/IL-8, IL-1 α, Keratin 8/18, MMP-1, MMP-3, MMP-9, PAI-I, SRB, tPA, uPA
BFNoEpithelial Biology, Lung BiologyBronchial epithelial cells + Dermal fibroblastsCCL2/MCP-1, CCL26/Eotaxin-3, CD106/VCAM-1, CD54/ICAM-1, CD90, CXCL8/IL-8, IL-1 α, Keratin 8/18, MMP-1, MMP-3, MMP-9, PAI-I, SRB, tPA, uPA
BTAllergy, Asthma, Autoimmunity, OncologyB cells + Peripheral blood mononuclear cellsB cell Proliferation, PBMC Cytotoxicity, Secreted IgG, sIL-17A, sIL-17F, sIL-2, sIL-6, sTNF-α
BTNoAllergy, Asthma, Autoimmunity, OncologyB cells + Peripheral blood mononuclear cellsB cell Proliferation, PBMC Cytotoxicity, Secreted IgG, sIL-17A, sIL-17F, sIL-2, sIL-6, sTNF-α
CAEC3CCardiovascular Disease, Chronic InflammationCoronary artery endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD54/ICAM-1, CD62E/E-Selectin, CD87/uPAR, CXCL8/IL-8, CXCL9/MIG, HLA-DR, PAI-I, Proliferation, SRB
CASM3CCardiovascular Inflammation, RestenosisCoronary artery smooth muscle cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD87/uPAR, CXCL8/IL-8, CXCL9/MIG, HLA-DR, IL-6, LDLR, M-CSF, PAI-I, Proliferation, Serum Amyloid A, SRB
CASMNoVascular BiologyCoronary artery smooth muscle cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD87/uPAR, CXCL8/IL-8, CXCL9/MIG, HLA-DR, IL-6, LDLR, M-CSF, PAI-I, Proliferation, Serum Amyloid A, SRB
HDF3CChronic Inflammation, FibrosisDermal fibroblastsCCL2/MCP-1, CD106/VCAM-1, CD54/ICAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, CXCL8/IL-8, CXCL9/MIG, EGFR, M-CSF, MMP-1, PAI-I, Proliferation_72hr, SRB, TIMP-1, TIMP-2
HDF3CGFChronic Inflammation, FibrosisDermal fibroblastsCCL2/MCP-1, CD106/VCAM-1, CD54/ICAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, CXCL8/IL-8, CXCL9/MIG, EGFR, M-CSF, MMP-1, PAI-I, Proliferation_72hr, SRB, TIMP-1, TIMP-2
HDFLPSAutoimmune Disease, Chronic Inflammation, Infection responsesDermal fibroblasts + Peripheral blood mononuclear cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, M-CSF, MMP-1, sIL-10, sIL-17A, sIL-17F, sIL-2, sIL-6, SRB, sTGF-β 1, sTNF-α, sVEGF
HDFNoFibroblast BiologyDermal fibroblastsCCL2/MCP-1, CD106/VCAM-1, CD54/ICAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, CXCL8/IL-8, CXCL9/MIG, EGFR, M-CSF, MMP-1, PAI-I, Proliferation_72hr, SRB, TIMP-1, TIMP-2
HDFPNoImmune BiologyDermal fibroblasts + Peripheral blood mononuclear cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, M-CSF, MMP-1, sIL-10, sIL-17A, sIL-17F, sIL-2, sIL-6, SRB, sTGF-β 1, sTNF-α, sVEGF
HDFSAgAutoimmune Disease, Chronic Inflammation, Rheumatoid ArthritisDermal fibroblasts + Peripheral blood mononuclear cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, M-CSF, MMP-1, sIL-10, sIL-17A, sIL-17F, sIL-2, sIL-6, SRB, sTGF-β 1, sTNF-α, sVEGF
HNoVascular BiologyVenular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD54/ICAM-1, CD62E/E-Selectin, CD87/uPAR, CXCL8/IL-8, CXCL9/MIG, HLA-DR, Proliferation, SRB
HPNoImmune Biology, Vascular BiologyPeripheral blood mononuclear cells + Venular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD38, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, CXCL9/MIG, M-CSF, sPGE2, SRB, sTNF-α
HSM3CCardiovascular Inflammation, RestenosisVascular smooth muscle cells + Venular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD40, CD54/ICAM-1, CD62E/E-Selectin, CD87/uPAR, Collagen I, Collagen IV, CXCL8/IL-8, CXCL9/MIG, Endothelin-1, HLA-DR, LDLR, M-CSF, PAI-I, Serum Amyloid A, SRB
K3CTDermatitis, Psoriasis, Skin BiologyKeratinocytesCCL2/MCP-1, CD54/ICAM-1, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, IL-1 α, MMP-9, PAI-I, SRB, TIMP-2, uPA
KF3CTDermatitis, PsoriasisDermal fibroblasts + KeratinocytesCCL2/MCP-1, CD54/ICAM-1, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, IL-1 α, MMP-9, PAI-I, SRB, TIMP-2, uPA
KFNoSkin BiologyDermal fibroblasts + KeratinocytesCCL2/MCP-1, CD54/ICAM-1, CXCL10/IP-10, CXCL8/IL-8, CXCL9/MIG, IL-1 α, MMP-9, PAI-I, SRB, TIMP-2, uPA
LPSCardiovascular Disease, Chronic InflammationPeripheral blood mononuclear cells + Venular endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, IL-1 α, M-CSF, sPGE2, SRB, sTNF-α
MyoFChronic Inflammation, Fibrosis, Matrix Remodeling, Wound HealingLung fibroblastsbFGF, CD106/VCAM-1, Collagen I, Collagen III, Collagen IV, CXCL8/IL-8, Decorin, MMP-1, PAI-I, SRB, TIMP-1, α-SM Actin
MyoFNoFibroblast BiologyLung fibroblastsbFGF, CD106/VCAM-1, Collagen I, Collagen III, Collagen IV, CXCL8/IL-8, Decorin, MMP-1, PAI-I, SRB, TIMP-1, α-SM Actin
REMyoFChronic Inflammation, Matrix Remodeling, Renal Fibrosis, Wound HealingLung fibroblasts + Renal proximal tubule epithelial cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, E-Cadherin, EGFR, Keratin 8/18, M-CSF, MMP-1, MMP-9, N-Cadherin, PAI-I, sIL-6, sIL-8, SRB, sVEGF, TIMP-1, tPA, uPA, α-SM Actin
REMyoFNoRenal BiologyLung fibroblasts + Renal proximal tubule epithelial cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, E-Cadherin, EGFR, Keratin 8/18, M-CSF, MMP-1, MMP-9, N-Cadherin, PAI-I, sIL-6, sIL-8, SRB, sVEGF, TIMP-1, tPA, uPA, α-SM Actin
SAEMyoFChronic Inflammation, Matrix Remodeling, Pulmonary Fibrosis, Wound HealingLung fibroblasts + Small airway epithelial cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, E-Cadherin, EGFR, M-CSF, MMP-1, MMP-9, N-Cadherin, PAI-I, sIL-6, sIL-8, SRB, sVEGF, TIMP-1, uPA, α-SM Actin
SAEMyoFNoPulmonary BiologyLung fibroblasts + Small airway epithelial cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, E-Cadherin, EGFR, M-CSF, MMP-1, MMP-9, N-Cadherin, PAI-I, sIL-6, sIL-8, SRB, sVEGF, TIMP-1, uPA, α-SM Actin
SAgAutoimmune Disease, Chronic InflammationPeripheral blood mononuclear cells + Venular endothelial cellsCCL2/MCP-1, CD38, CD40, CD62E/E-Selectin, CD69, CXCL8/IL-8, CXCL9/MIG, PBMC Cytotoxicity, Proliferation, SRB
SkMCMuscle BiologySkeletal muscle cellsGlycogen, SRB
SM3CCardiovascular Inflammation, RestenosisVascular smooth muscle cellsCCL2/MCP-1, CD106/VCAM-1, CD141/Thrombomodulin, CD142/Tissue Factor, CD87/uPAR, Collagen I, Collagen IV, CXCL8/IL-8, CXCL9/MIG, HLA-DR, IL-6, LDLR, M-CSF, PAI-I, Proliferation, Serum Amyloid A, SRB
StroCHost Stromal Biology, Host Stromal-Tumor Microenvironment, Oncology, Oncology - CRC, Wound HealingPeripheral blood mononuclear cells + Primary human fibroblastsCD106/VCAM-1, CD87/uPAR, CEACAM5/CD66e, Collagen I, Collagen III, CXCL10/IP-10, Keratin 20, MMP-9, PAI-I, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-17A, sIL-2, sIL-6, SRB, sTNF-α, sVEGF, TIMP-2, tPA, uPA
StroHT29Host Stromal-Tumor Microenvironment, Oncology, Oncology - CRCHT-29 colon adenocarcinoma cell line + Peripheral blood mononuclear cells + Primary human fibroblastsCD106/VCAM-1, CD87/uPAR, CEACAM5/CD66e, Collagen I, Collagen III, CXCL10/IP-10, Keratin 20, MMP-9, PAI-I, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-17A, sIL-2, sIL-6, SRB, sTNF-α, sVEGF, TIMP-2, tPA, uPA
StroLHost Stromal-Tumor Microenvironment, Oncology, Oncology - NSCLCPeripheral blood mononuclear cells + Primary human fibroblastsCD106/VCAM-1, CD87/uPAR, Collagen III, CXCL10/IP-10, EGFR, HGF, PAI-I, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-13, sIL-17A, sIL-2, sIL-4, sIL-6, sMDC, sPGE2, SRB, sTNF-α, sVEGF, tPA, uPA
StroNSCLCHost Stromal-Tumor Microenvironment, Oncology, Oncology - NSCLCH1299 NSCLC cell line + Peripheral blood mononuclear cells + Primary human fibroblastsCD106/VCAM-1, CD87/uPAR, Collagen III, CXCL10/IP-10, EGFR, HGF, PAI-I, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-13, sIL-17A, sIL-2, sIL-4, sIL-6, sMDC, sPGE2, SRB, sTNF-α, sVEGF, tPA, uPA
VascCHost Vascular Biology, Host Vascular-Tumor Microenvironment, Inflammation, Oncology, Oncology - CRCPeripheral blood mononuclear cells + Primary human endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD40, CD69, CD87/uPAR, CEACAM5/CD66e, Collagen IV, CXCL10/IP-10, CXCL9/MIG, Keratin 20, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-17A, sIL-2, sIL-6, SRB, sTNF-α
VascHT29Host Vascular-Tumor Microenvironment, Oncology, Oncology - CRCHT-29 colon adenocarcinoma cell line + Peripheral blood mononuclear cells + Primary human endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD40, CD69, CD87/uPAR, CEACAM5/CD66e, Collagen IV, CXCL10/IP-10, CXCL9/MIG, Keratin 20, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-17A, sIL-2, sIL-6, SRB, sTNF-α
VascLHost Vascular-Tumor Microenvironment, Oncology, Oncology - NSCLCPeripheral blood mononuclear cells + Primary human endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD40, CD69, CD87/uPAR, CXCL10/IP-10, PAI-I, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-13, sIL-17A, sIL-2, sIL-4, sIL-6, sMDC, SRB, sTNF-α
VascNSCLCHost Vascular-Tumor Microenvironment, Oncology, Oncology - NSCLCH1299 NSCLC cell line + Peripheral blood mononuclear cells + Primary human endothelial cellsCCL2/MCP-1, CD106/VCAM-1, CD40, CD69, CD87/uPAR, CXCL10/IP-10, PAI-I, PBMC Cytotoxicity, sGranzyme B, sIFN-γ, sIL-10, sIL-13, sIL-17A, sIL-2, sIL-4, sIL-6, sMDC, SRB, sTNF-α