The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells.

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Home > References > 2008 > The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells.

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The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells.

Luqman, M., Klabunde, S., Lin, K., Georgakis, G.V., Cherukuri, A., Holash, J., Goldbeck, C., Xu, X., Kadel, E.E. 3rd, Lee, S.H., Aukerman, S.L., Jallal, B., Aziz, N., Weng, W.K., Wierda, W., O'Brien, S., Younes, A.

Journal		Blood
Species
Analytes Measured		GM-CSF , IL-10 , IL-6 , IL-8
Matrix Tested		Peripheral blood mononuclear cell (PBMC) culture supernatants

Year		2008
Volume		112
Page Numbers		711-720
Application		Cytokines and Chemokines

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder characterized by the surface expression of CD20, CD5 antigens, as well as the receptor CD40. Activation of CD40 by its ligand (CD40L) induces proliferation and rescues the cells from spontaneous and chemotherapy-induced apoptosis. CD40 activation also induces secretion of cytokines, such as IL-6, IL-10, TNF-alpha, IL-8, and GM-CSF, which are involved in tumor cell survival, migration, and interaction with cells in the tumor microenvironment. Here we demonstrate that in primary B-CLL tumor cells, the novel antagonist anti-CD40 monoclonal antibody, HCD122, inhibits CD40L-induced activation of signaling pathways, proliferation and survival, and secretion of cytokines. Furthermore, HCD122 is also a potent mediator of antibody-dependent cellular cytotoxicity (ADCC), lysing B-CLL cells more efficiently than rituximab in vitro, despite a significantly higher number of cell surface CD20 binding sites compared with CD40. Unlike rituximab, however, HCD122 (formerly CHIR-12.12) does not internalize upon binding to the cells. Our data suggest that HCD122 may inhibit B-CLL growth by blocking CD40 signaling and by ADCC-mediated cell lysis.

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U-PLEX NHP IL-8 384-Well Assay IL-8 \| Non-human primate Singleplex
U-PLEX NHP IL-6 384-Well Assay IL-6 \| Non-human primate Singleplex
U-PLEX Custom Metabolic Group 1 (mouse) 384-well 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 Biomarker Group 1 (NHP) 384-well 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 Human GM-CSF 384-Well Assay GM-CSF \| Human Singleplex
U-PLEX Human IL-10 384-Well Assay IL-10 \| Human Singleplex
U-PLEX Human IL-8 384-Well Assay IL-8 \| Human Singleplex
U-PLEX Human IL-6 384-Well Assay IL-6 \| Human Singleplex
U-PLEX Custom Metabolic Group 1 (human) 384-well 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 Biomarker Group 1 (human) 384-well 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
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
U-PLEX Macrophage M2 Combo 1 (mouse) IL-4, IL-10, IL-13, MDC, TARC \| Mouse Multiplex
S-PLEX NHP IL-6 Kit IL-6 \| Non-human primate Singleplex
S-PLEX Human IL-6 Kit IL-6 \| Human Singleplex
S-PLEX Human IL-10 Kit IL-10 \| Human Singleplex
S-PLEX Human GM-CSF Kit GM-CSF \| Human Singleplex
U-PLEX CAR-T Cell Combo 1 (human) GM-CSF, Granzyme A, Granzyme B, IFN-γ, IL-2, TNF-α \| Human 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 M1 Combo 1 (human) IL-1β, IL-6, IL-12p70, IL-18, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
V-PLEX Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| 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 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
V-PLEX Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
U-PLEX NHP IL-8 Assay IL-8 \| Non-human primate Singleplex
U-PLEX NHP IL-6 Assay IL-6 \| Non-human primate Singleplex
U-PLEX NHP IL-10 Assay IL-10 \| Non-human primate Singleplex
U-PLEX NHP GM-CSF Assay GM-CSF \| Non-human primate Singleplex
U-PLEX Mouse GM-CSF Assay GM-CSF \| Mouse Singleplex
U-PLEX Mouse IL-10 Assay IL-10 \| Mouse Singleplex
U-PLEX Mouse IL-6 Assay IL-6 \| Mouse Singleplex
U-PLEX Human IL-6 Assay IL-6 \| Human Singleplex
U-PLEX Human IL-8 Assay IL-8 \| Human Singleplex
U-PLEX Human IL-10 Assay IL-10 \| Human Singleplex
U-PLEX Human GM-CSF Assay GM-CSF \| Human Singleplex
R-PLEX Rat GM-CSF Assay GM-CSF \| Rat Singleplex
R-PLEX Rat IL-10 Assay IL-10 \| Rat Singleplex
R-PLEX Rat IL-6 Assay IL-6 \| Rat Singleplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays Mouse 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 Hormones 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 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 Adipokine Combo 1 (human) BDNF, β-NGF, IL-1β, IL-6, IL-8, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Human Multiplex
R-PLEX Rat GM-CSF Antibody Set GM-CSF \| Rat
R-PLEX Rat IL-6 Antibody Set IL-6 \| Rat
R-PLEX Rat IL-10 Antibody Set IL-10 \| Rat
V-PLEX Plus Mouse Cytokine 19-Plex Kit IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α \| Mouse Multiplex
V-PLEX Mouse Cytokine 19-Plex Kit IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, 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 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 (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 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 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 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 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
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
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
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
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
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
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, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human 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
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
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
U-PLEX Proinflam Combo 4 (human) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
U-PLEX Proinflam Combo 3 (human) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex
U-PLEX Human GM-CSF Antibody Set GM-CSF \| Human
U-PLEX Human IL-8 Antibody Set IL-8 \| Human
U-PLEX Human IL-6 Antibody Set IL-6 \| Human
U-PLEX Human IL-10 Antibody Set IL-10 \| Human
U-PLEX Mouse GM-CSF Antibody Set GM-CSF \| Mouse
U-PLEX Mouse IL-10 Antibody Set IL-10 \| Mouse
U-PLEX Mouse IL-6 Antibody Set IL-6 \| Mouse
V-PLEX Proinflammatory Panel 2 Rat Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α \| Rat Multiplex
V-PLEX Plus Proinflammatory Panel 2 Rat Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α \| Rat Multiplex
V-PLEX Plus Human Biomarker 39-Plex Kit CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 \| Human Multiplex
V-PLEX Human Biomarker 39-Plex Kit CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 \| Human Multiplex
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The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells.

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