Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody.

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Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody.

Guo, Y., Hill, A.A., Ramsey, R.C., Immermann, F.W., Corcoran, C., Young, D., Lavallie, E.R., Ryan, M., Bouchard, T., Pfeifer, R., Warner, G., Bologna, M., Bloom, L., O'Toole, M.

Journal		J Transl Med.
Species
Analytes Measured		IL-10 , IL-12 p70 , IL-13 , IL-2 , IL-4 , IL-5 , IL-6 , IL-8 , MCP-1
Matrix Tested		Peripheral blood mononuclear cell (PBMC) culture supernatants

Year		2010
Volume		8
Page Numbers
Application		Cytokines and Chemokines

Abstract

BACKGROUND: Selective neutralization of the IL21/IL21R signaling pathway is a promising approach for the treatment of a variety of autoimmune diseases. Ab-01 is a human neutralizing anti-IL21R antibody. In order to ensure that the activities of Ab-01 are restricted to neutralization even under in vitro cross-linking and in vivo conditions, a comprehensive assessment of agonistic potential of Ab-01 was undertaken.

METHODS: In vitro antibody cross-linking and cell culture protocols reported for studies with a human agonistic antibody, TGN1412, were followed for Ab-01. rhIL21, the agonist ligand of the targeted receptor, and cross-linked anti-CD28 were used as positive controls for signal transduction. In vivo agonistic potential of Ab-01 was assessed by measuring expression levels of cytokine storm-associated and IL21 pathway genes in blood of cynomolgus monkeys before and after IV administration of Ab-01.

RESULTS: Using a comprehensive set of assays that detected multiple activation signals in the presence of the positive control agonists, in vitro Ab-01-dependent activation was not detected in either PBMCs or the rhIL21-responsive cell line Daudi. Furthermore, no difference in gene expression levels was detected in blood before and after in vivo Ab-01 dosing of cynomolgus monkeys.

CONCLUSIONS: Despite efforts to intentionally force an agonistic signal from Ab-01, none could be detected.

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V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex		NEW
V-PLEX Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex		NEW
V-PLEX Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex		NEW
V-PLEX Plus Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Proinflammatory Panel 1 NHP Kit IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Plus Proinflammatory Panel 1 Human Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Proinflammatory Panel 1 NHP Kit IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Plus NHP IL-10 Kit IL-10 \| Non-human primate Singleplex		NEW
V-PLEX Plus Human IL-13 Kit IL-13 \| Human Singleplex		NEW
V-PLEX Plus Human IL-10 Kit IL-10 \| Human Singleplex		NEW
V-PLEX Plus Human IL-4 Kit IL-4 \| Human Singleplex		NEW
V-PLEX NHP IL-10 Kit IL-10 \| Non-human primate Singleplex		NEW
V-PLEX Human IL-13 Kit IL-13 \| Human Singleplex		NEW
V-PLEX Human IL-10 Kit IL-10 \| Human Singleplex		NEW
V-PLEX Human IL-4 Kit IL-4 \| Human Singleplex		NEW
V-PLEX Proinflammatory Panel 1 Human Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Human Proinflam. Panel II (4-Plex) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Human Proinflam. Panel I (4-Plex) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
V-PLEX Human Proinflammatory Panel II (4-Plex) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Human Proinflammatory Panel I (4-Plex) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
R-PLEX Rabbit IL-6 Assay IL-6 \| Rabbit Singleplex		NEW
U-PLEX Biomarker Group 1 (NHP) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 \| Non-human primate Multiplex
U-PLEX Custom Biomarker Group 1 (human) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Biomarker Group 1 (mouse) Assays 6CKine/CCL21, BAFF, BCA-1/BLC, CD40/TNFRSF5, Eotaxin, EPO, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), NGAL/LCN2, RANTES, SDF-1α, TARC, TNF-α, TNF-RI, VEGF-A \| Mouse Multiplex
U-PLEX Custom Metabolic Group 1 (human) Assays BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays BAFF, BCA-1/BLC, BDNF, CD40/TNFRSF5, C-Peptide, Eotaxin, EPO, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, Insulin, IP-10, KC/GRO, Leptin, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), PYY (total), RANTES, TARC, TNF-α, VEGF-A \| Mouse Multiplex
U-PLEX Alzheimer's Disease Combo 1 (human) Eotaxin, IL-1α, IL-12/IL-23p40, IL-16, IL-17A, MCP-1, MDC, MIF, SDF-1α, YKL-40 \| Human Multiplex
U-PLEX Multiple Sclerosis Combo 1 (human) CTACK, Fractalkine, GRO-α, IL-7, IL-12/IL-23p40, IP-10, MCP-1, MIP-1β, MIP-3α \| Human Multiplex
U-PLEX TBI Combo 1 (human) CD40L (soluble), Fractalkine, IFN-γ, IL-1β, IL-6, IL-18, MCP-1, RANKL/TNFSF11, TNF-α, VEGF-D \| Human Multiplex
U-PLEX Chemokine Combo (mouse) IP-10, KC/GRO, MCP-1, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (human) Eotaxin, Eotaxin-2, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Human Multiplex		NEW
U-PLEX Chemokine Combo 1 (mouse) IP-10, KC/GRO, MCP-1, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (NHP) Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Non-human primate Multiplex		NEW
U-PLEX Cytokine Combo 1 (human) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex		NEW
U-PLEX Cytokine Combo 1 (NHP) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex		NEW
U-PLEX Macrophage M1 Combo 1 (human) IL-1β, IL-6, IL-12p70, IL-18, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Human Multiplex
U-PLEX Macrophage M1 Combo 1 (mouse) IL-1β, IL-6, IL-12p70, IL-15, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Mouse Multiplex
U-PLEX Macrophage M2 Combo 1 (human) Eotaxin-2, IL-4, IL-10, IL-13, M-CSF, MDC, TARC \| Human Multiplex
U-PLEX Macrophage M2 Combo 1 (mouse) IL-4, IL-10, IL-13, MDC, TARC \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (human) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
U-PLEX Proinflam Combo 1 (mouse) IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12p70, IL-17A, IP-10, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α \| Non-human primate Multiplex		NEW
U-PLEX Proinflam Combo 3 (human) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
U-PLEX Proinflam Combo 4 (human) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
U-PLEX T-Cell Combo (human) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Human Multiplex
U-PLEX T-Cell Combo (mouse) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Mouse Multiplex
U-PLEX T-Cell Combo (NHP) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-22, MIP-3α, TNF-α \| Non-human primate Multiplex
U-PLEX TH1/TH2 Combo (human) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
U-PLEX TH1/TH2 Combo (mouse) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, KC/GRO, TNF-α \| Mouse Multiplex		NEW
U-PLEX TH1/TH2 Combo (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, TNF-α \| Non-human primate Multiplex
U-PLEX TH17 Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, TNF-α \| Non-human primate Multiplex
U-PLEX TH17 Combo 2 (human) IFN-γ, IL-1β, IL-6, IL-10, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, TNF-α \| Human Multiplex
U-PLEX TH17 Combo 2 (mouse) IFN-γ, IL-1β, IL-6, IL-17A, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, TNF-α \| Mouse Multiplex
U-PLEX Viral Combo 1 (human) G-CSF, GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Human Multiplex
U-PLEX Viral Combo 1 (NHP) G-CSF, GM-CSF, IFN-α2a, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Non-human primate Multiplex
U-PLEX Adipokine Combo 1 (human) BDNF, β-NGF, IL-1β, IL-6, IL-8, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Human Multiplex
U-PLEX Adipokine Combo 1 (mouse) BDNF, IL-1β, IL-6, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Metabolic Hormone Combo 1 (mouse) C-Peptide, Ghrelin (active), GLP-1 (active), Glucagon, IL-6, Insulin, Leptin, MCP-1, PYY (total), TNF-α \| Mouse Multiplex
U-PLEX CAR-T Cell Combo 2 (human) GM-CSF, Granzyme A, Granzyme B, IFN-γ, IL-2, Perforin, TNF-α \| Human Multiplex
U-PLEX CAR-T Cell Efficacy Combo 1 (human) Granzyme B, IFN-γ, IL-2, IL-6, IL-12p70, IP-10, Perforin, TNF-α \| Human Multiplex
U-PLEX CAR-T Cell Safety Combo 1 (human) GM-CSF, IFN-γ, IL-1β, IL-6, IL-10, MCP-1, TNF-α \| Human Multiplex
U-PLEX Oncolysis Combo 1 (human) CTLA-4, IFN-α2a, IFN-β, IL-1β, IL-2Rα, IL-6, IL-8, IP-10, LAG3, MIP-1α, PD1 (epitope 1), TIGIT \| Human Multiplex
U-PLEX Proinflam Combo 2 (human) GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 \| Human Multiplex		NEW
S-PLEX Custom Human Biomarkers Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF-α \| Human Multiplex
S-PLEX Proinflammatory Panel 1 (human) Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF-α \| Human Multiplex
Human MCP-1 Antibody MCP-1 \| Human
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Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody.

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