Alternative Names
CXCR5; chemokine (C-X-C motif) receptor 5; BLR1, Burkitt lymphoma receptor 1, GTP binding protein (chemokine (C X C motif) receptor 5) , Burkitt lymphoma receptor 1, GTP binding protein; C-X-C chemokine receptor type 5; CD185; MDR15; CXC-R5; CXCR-5; MDR
Pathway
Chemokine receptors bind chemokines, organism-specific biosystem; Chemokine signaling pathway, organism-specific biosystem; Chemokine signaling pathway, conserved biosystem; Class A/1 (Rhodopsin-like receptors), organism-specific biosystem; Cytokine-cytok
A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis
Cohen S, Beebe JS, Chindalore V, Guan S, Hassan-Zahraee M, Saxena M, Xi L, Hyde C, Koride S, Levin R, Lubaczewski S, Salganik M, Sloan A, Stevens E, Peeva E, Vincent MS, Martin DA, Chu M
Applications: FCM
Reactive species: Human
"Abstract: Background: The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects."
Article snippet: Whole blood was stained with an antibody cocktail containing anti-human monoclonal antibodies against CD45-AF700 and CCR6-BV421 (***), CD3-APC-H7, CD4 PerCPCy5.5, CD45RO-BV510, PD1-PE, ICOS-AF647, CD183- PE-Cy7 (***), and a non-drug competitive CXCR5-AF488 antibody (Creative Diagnostics, Shirley, NY), for 20 min at room temperature. Red blood cells were lyzed using FACSLyse (***), washed with staining bufer, and data were immediately acquired on a BD FACSCanto II fow cytometer.