scholarly journals Protective effect of neutralizing anti-IL-18α monoclonal antibody on a mouse model of acute graft-versus-host disease

2015 ◽  
Vol 34 (4) ◽  
pp. 2031-2039 ◽  
Author(s):  
XIAOCUI LI ◽  
CUIPING ZHANG ◽  
WEI CHEN ◽  
BIN PAN ◽  
FANYUN KONG ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mouse Model ◽  
Protective Effect ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals Compound a Increases Cell Infiltration in Target Organs of Acute Graft-versus-Host Disease (aGVHD) in a Mouse Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4237
Author(s):  
Abdellatif Bouazzaoui ◽  
Ahmed A. H. Abdellatif ◽  
Faisal A. Al-Allaf ◽  
Neda M. Bogari ◽  
Mohiuddin M. Taher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Graft Versus Host Disease ◽  
Cell Infiltration ◽  
Compound A ◽  
Host Disease ◽  
Graft Versus Host ◽  
Target Organs ◽  
Acute Graft

Systemic steroids are used to treat acute graft-versus-host disease (aGVHD) caused by allogenic bone marrow transplantation (allo-BMT); however, their prolonged use results in complications. Hence, new agents for treating aGVHD are required. Recently, a new compound A (CpdA), with anti-inflammatory activity and reduced side effects compared to steroids, has been identified. Here, we aimed to determine whether CpdA can improve the outcome of aGVHD when administered after transplantation in a mouse model (C57BL/6 in B6D2F1). After conditioning with 9Gy total body irradiation, mice were infused with bone marrow (BM) cells and splenocytes from either syngeneic (B6D2F1) or allogeneic (C57BL/6) donors. The animals were subsequently treated (3 days/week) with 7.5 mg/kg CpdA from day +15 to day +28; the controls received 0.9% NaCl. Thereafter, the incidence and severity of aGVHD in aGVHD target organs were analyzed. Survival and clinical scores did not differ significantly; however, CpdA-treated animals showed high cell infiltration in the target organs. In bulk mixed lymphocyte reactions, CpdA treatment reduced the cell proliferation and expression of inflammatory cytokines and chemokines compared to controls, whereas levels of TNF, IL-23, chemokines, and chemokine receptors increased. CpdA significantly reduced proliferation in vitro but increased T cell infiltration in target organs.

PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE BY MONOCLONAL ANTIBODY TO INTERLEUKIN-2 RECEPTOR

The Lancet ◽  
1989 ◽  
Vol 333 (8650) ◽  
pp. 1333-1334 ◽  
Author(s):  
Didier Blaise ◽  
Dominique Maraninchi ◽  
Claude Mawas ◽  
AnneMarie Stoppa ◽  
Michel Hirn ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor

1991 ◽  
Vol 34 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Dietrich W. Beelen ◽  
Hans Grosse-Wilde ◽  
Ursula Ryschka ◽  
Klaus Quabeck ◽  
Herbert G. Sayer ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Initial Treatment ◽  
Cell Receptor ◽  
Murine Monoclonal Antibody ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals A novel mouse model of acute graft-versus-host disease based on chemotherapy conditioning and G-CSF mobilized graft

2019 ◽  
Vol 55 (3) ◽  
pp. 570-577
Author(s):  
Yishan Ye ◽  
Laure Ricard ◽  
Nicolas Stocker ◽  
Mohamad Mohty ◽  
Béatrice Gaugler ◽  
...  
Keyword(s):  
Mouse Model ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10) [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
P Herve ◽  
J Wijdenes ◽  
JP Bergerat ◽  
P Bordigoni ◽  
N Milpied ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Host Disease ◽  
Graft Versus Host ◽  
In Vivo Administration ◽  
Acute Graft ◽  
Receptor Monoclonal Antibody

Abstract In a multicenter pilot study, 32 patients showing steroid-resistant acute graft-versus-host disease (GVHD) were treated by in vivo administration of anti-interleukin-2 (IL-2) receptor monoclonal antibody (MoAb B-B10). Twenty-three patients received marrow from HLA- matched related donors, four from matched unrelated donors and five from partially matched related donors. The overall grade of GVHD was II in 16 patients, III in two, and IV in five. Five milligrams of B-B10 MoAb was infused in bolus daily for 10 days and then every second day for a further 10 days in an attempt to reduce GVHD recurrence. No clinical side effects were noted during the B-B10 treatment period. A complete response (CR) acute GVHD was achieved in 21 patients (65.6%). Six patients (18.7%) showed partial improvement (PR) and 5 patients (15.6%) no response (NR). A significant factor associated with GVHD response was the delay between the onset of the GVHD and the first day of B-B10 infusion. The earlier B-B10 was introduced, the greater the probability of CR (P = .03). There was no correlation between the serum B-B10 level and GVHD response (P = .69). There was, however, a significant correlation between the clinical response and the B-B10 kinetics as a function of time: serum B-B10 levels attained a plateau level more rapidly in the CR group than in the PR/NR group. Among the 26 complete and partial evaluable responders, GVHD recurred in 10 cases (38.4%). Host anti-B-B10 MoAb immune response occurred in only one (7.1%) of the 14 patients analyzed. Fourteen of the 32 patients (43.7%) are currently alive between 2 and 14 months after GVHD treatment with B- B10 was completed.

Rituximab Reduces the Incidence of Acute Graft Versus Host Disease and Delays CD3+CD4+ Lymphocyte Recovery.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5005-5005 ◽  
Author(s):  
Maximilian Christopeit ◽  
Vincent Schuette ◽  
Gerhard Behre
Keyword(s):  
Monoclonal Antibody ◽  
B Lymphocytes ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cd4 Lymphocyte ◽  
Antigen Presenting ◽  
Cd4 Lymphocytes ◽  
Acute Graft ◽  
Graft Versus Tumor Effect

Abstract The monoclonal antibody Rituximab has been successfully used to treat steroidrefractory chronic graft versus host disease (cGvH) after allogeneic stem cell transplantation (SCT). We hypothesized that Rituximab might reduce the incidence of aGvH. We found that patients conditioned with a regimen containing Rituximab experienced significantly less aGvH when compared to a regimen without Rituximab (23.1% versus 66.7%, p = 0.032). Furthermore did we find that the recovery of CD3+CD4+ lymphocytes was delayed following administration of Rituximab. As expected, patients were devoid of CD19+CD20+ B lymphocytes after administration of Rituximab; interestingly, both the recovery of CD3+CD8+ lymphocytes and CD16+CD56+ NK cells did not differ between patients receiving Rituximab and Rituximab-naíve patients. Furthermore, our data revealed a significant correlation of the transplants CD34+ HSC content with the occurrence of aGvH (p = 0.031) but only a trend towards a correlation of CD3+ cells with the occurrence of aGvH (p = 0.274). Taken together, our data establish a mechanism of how Rituximab might reduce the incidence of aGvH next to depleting host and perhaps donor antigen presenting cells. It remains to be elucidated whether this effect translates to a graft versus tumor effect and to survival as well.

A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2712-2719 ◽  
Author(s):  
Paul A. Carpenter ◽  
Frederick R. Appelbaum ◽  
Lawrence Corey ◽  
H. Joachim Deeg ◽  
Kris Doney ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Preemptive Therapy ◽  
Multiple Dosing ◽  
Activated T Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Ebv Dna ◽  
Acute Graft

Abstract Visilizumab is a humanized anti-CD3 monoclonal antibody characterized by a mutated IgG2 isotype, lack of binding to Fcγ-receptors, and ability to induce apoptosis selectively in activated T cells. To test pharmacokinetics, safety, and immunosuppressive activity of visilizumab, 17 patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD) were enrolled in a phase 1 study. Six patients were given 7 doses of visilizumab (0.25 or 1.0 mg/m2) on days 1, 3, 5, 7, 9, 11, and 13. Because multiple doses of 1 mg/m2 caused delayed visilizumab accumulation and prolonged lymphopenia, the next 11 patients received a single dose of 3.0 mg/m2 on day 1. GVHD improved in all patients; 15 were evaluable through day 42. Multiple dosing resulted in 1 of 6 complete responses (CRs) and 5 partial responses (PRs), but all 6 patients died at a median of 87 days after starting visilizumab therapy. Single dosing resulted in 6 of 9 CRs, 3 PRs, and 7 of 11 patients surviving after 260 to 490 days (median, 359 days; P = .03). There were no allergic reactions and 3 grade 1 acute infusional toxicities. Plasma Epstein-Barr virus (EBV) DNA titers more than 1000 copies/mL and posttransplant lymphoproliferative disease (PTLD) developed in 2 of the first 7 patients. Based on rising EBV DNA titers, 5 of the next 10 patients were given the B cell–specific monoclonal antibody, rituximab. EBV DNA became undetectable and no overt PTLD developed. Visilizumab is well tolerated and has activity in advanced GVHD. A phase 2 study incorporating preemptive therapy for PTLD is warranted to determine the efficacy of visilizumab in GVHD.

Sign in / Sign up

Export Citation Format

Share Document