Afuco™ Anti-Human CCR5 ADCC Recombinant Antibody (HGS004), ADCC Enhanced (CAT#: AFC-097CL)

Anti-CCR5 ADCC Enhanced Antibody (HGS004) is an ADCC enhanced antibody produced by our Afuco™ platform. HGS004 is a human immunoglobulin (Ig) G4 monoclonal antibody against CCR5. HGS004 binds to and inhibits the activity of the CCR5 receptor on the cell surface. HIV uses both the CCR5 and the CD4 receptors to gain entry to the cell, but CCR5 is the primary receptor enabling HIV transmission and replication from the early stages of infection through to progression to AIDS.


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Figure 1 Serum concentration of HGS004.

Figure 1 Serum concentration of HGS004.

A) and receptor occupancy (RO) of CD4 cells expressing CCR5 in peripheral blood by HGS004 (B) in subjects receiving a single intravenous infusion of 0.4, 2, 8, 20, or 40 mg/kg.

Lalezari, J,Yadavalli,G.K.,Para,M.,Richmond,G.,DeJesus, E., Brown, S. J., & Lederman, M. M. (2008). Safety, Pharmacokinetics,and Antiviral Activity of HGS004,a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients.The Journal of infectious diseases,197(5),721-727.

Figure 2 Significant reductions in HIV-1 RNA were observed only in the higher-dose cohorts (8, 20, and 40 mg/kg)

Figure 2 Significant reductions in HIV-1 RNA were observed only in the higher-dose cohorts (8, 20, and 40 mg/kg)

A, Mean HIV-1 RNA reduction observed during a 56-day period in patients receiving a single intravenous infusion of HGS004 (0.4, 2, 8, 20, or 40 mg/kg), compared with placebo. B, HIV-1 RNA reduction in individual subjects receiving the maximum single intravenous dose of 40 mg/kg. DM refers to the 3 subjects who had dual/mixed (CXCR4/CCR5)-tropic isolates detected during the study.

Lalezari, J,Yadavalli,G.K.,Para,M.,Richmond,G.,DeJesus, E., Brown, S. J., & Lederman, M. M. (2008). Safety, Pharmacokinetics,and Antiviral Activity of HGS004,a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients.The Journal of infectious diseases,197(5),721-727.

Figure 3 Pharmacodynamics of HGS004.

Figure 3 Pharmacodynamics of HGS004.

A, Relationship of HIV-1 RNA reduction at day 14, serum HGS004 concentrations at day 14 (Cday14), and HIV-1 isolate susceptibility (IC90) in individual subjects. B, Relationship of HIV-1 RNA reduction at day 14 and drug exposure (area under the curve [AUC]) in individual subjects. EAUC50, AUC at 50% maximum effect; Emax, maximum effect.

Lalezari, J,Yadavalli,G.K.,Para,M.,Richmond,G.,DeJesus, E., Brown, S. J., & Lederman, M. M. (2008). Safety, Pharmacokinetics,and Antiviral Activity of HGS004,a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients.The Journal of infectious diseases,197(5),721-728.

Figure 4 the susceptibility of individual subject HIV-1 isolates to a more potent fully human monoclonal antibody (HGS101) was assessed.

Figure 4 the susceptibility of individual subject HIV-1 isolates to a more potent fully human monoclonal antibody (HGS101) was assessed.

Comparison of the potency of monoclonal antibodies HGS004 and HGS101 on the basis of clinical isolate IC90 values in individual subjects

Lalezari, J,Yadavalli,G.K.,Para,M.,Richmond,G.,DeJesus, E., Brown, S. J., & Lederman, M. M. (2008). Safety, Pharmacokinetics,and Antiviral Activity of HGS004,a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients.The Journal of infectious diseases,197(5),721-729.

Figure 5 The changes in CD4 and CD8 cell numbers from baseline.

Figure 5 The changes in CD4 and CD8 cell numbers from baseline.

Mean change in CD4 (A) and CD8 (B) cell counts from pretreatment levels during a 56-day period in subjects receiving a single intravenous infusion of HGS004 (0.4, 2, 8, 20, or 40 mg/kg) or placebo.

Lalezari, J,Yadavalli,G.K.,Para,M.,Richmond,G.,DeJesus, E., Brown, S. J., & Lederman, M. M. (2008). Safety, Pharmacokinetics,and Antiviral Activity of HGS004,a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients.The Journal of infectious diseases,197(5),721-730.

Figure 6 Antiviral interactions between HGS004 and MVC versus HGS004 and RAL against R5 HIV-1 in primary cells.

Figure 6 Antiviral interactions between HGS004 and MVC versus HGS004 and RAL against R5 HIV-1 in primary cells.

PHA-activated PBMCs infected with HIV-1 BaL (a) or HIV-1 CC1/85 (b) using an MOI of 0.001 were cultured in the presence of the indicated drug concentrations. Virus production was measured on day 7 by p24 ELISA. Inhibition data from replicates were plotted using GraphPad Prism software and EC50 values determined using variable slope non-linear regression analysis. MVC EC50s for BaL and CC1/85 were 0.74 and 0.34 nM, respectively; whereas RAL EC50s for BaL and CC1/85 were 4.3 and 1.1 nM, respectively (not shown). Upper panels: Dose response curves for HGS004, alone and in combination with MVC or RAL. At each MVC or RAL concentration, p24 inhibition by HGS004 was normalized to inhibition by MVC or RAL alone. Data points are means ± S.D. of duplicates. Lower panels: Three-dimensional analysis of viral inhibition by drug combinations. Percentage synergy obtained by each combination was plotted against HGS004 and MVC or RAL concentrations according to Prichard's synergy model. The 96% confidence interval synergy plots are shown. Percentage synergies at each 10% increment are shown in different color intensities. Note that the synergy plots included more drug concentrations than those shown in dose response curves. Data are representative of three independent experiments for BaL and two independent experiments for CC1/85, with PBMCs from different donors in each experiment.

Lalezari, J,Yadavalli,G.K.,Para,M.,Richmond,G.,DeJesus, E., Brown, S. J., & Lederman, M. M. (2008). Safety, Pharmacokinetics,and Antiviral Activity of HGS004,a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients.The Journal of infectious diseases,197(5),721-731.


Specifications

  • Host Species
  • Human
  • Derivation
  • Human
  • Type
  • ADCC enhanced antibody
  • Species Reactivity
  • Human
  • Related Disease
  • HIV Infection

Product Property

  • Purity
  • >97%, by SDS-PAGE under reducing conditions
  • Storage
  • ≤1 year at -20°C.

Target

  • Alternative Names
  • CCR5; chemokine (C-C motif) receptor 5 (gene/pseudogene); CKR5; CCR-5; CD195; CKR-5; CCCKR5; CMKBR5; IDDM22; CC-CKR-5; C-C chemokine receptor type 5; chemr13; HIV-1 fusion coreceptor; chemokine receptor CCR5; C-C motif chemokine receptor 5 A159A

Product Notes

This is a product of Creative Biolabs' Hi-Affi™ recombinant antibody portfolio, which has several benefits including:

• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production

See more details about Hi-Affi™ recombinant antibody benefits.

Downloads

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