+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease



A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease



Blood 95(12): 3693-3701



This study evaluated the anti-graft versus host disease (GVHD) potential of a combination of immunotoxins (IT), consisting of a murine CD3 (SPV-T3a) and CD7 (WT1) monoclonal antibody both conjugated to deglycosylated ricin A. In vitro efficacy data demonstrated that these IT act synergistically, resulting in an approximately 99% elimination of activated T cells at 10(-8 )mol/L (about 1.8 microg/mL). Because most natural killer (NK) cells are CD7(+), NK activity was inhibited as well. Apart from the killing mediated by ricin A, binding of SPV-T3a by itself impaired in vitro cytotoxic T-cell cytotoxicity. Flow cytometric analysis revealed that this was due to both modulation of the CD3/T-cell receptor complex and activation-induced cell death. These results warranted evaluation of the IT combination in patients with refractory acute GVHD in an ongoing pilot study. So far, 4 patients have been treated with 3 to 4 infusions of 2 or 4 mg/m(2) IT combination, administered intravenously at 48-hour intervals. The T(1/2) was 6.7 hours, and peak serum levels ranged from 258 to 3210 ng/mL. Drug-associated side effects were restricted to limited edema, fever, and a modest rise of creatine kinase levels. One patient developed low-titer antibodies against ricin A. Infusions were associated with an immediate drop of circulating T cells, followed by a more gradual but continuing elimination of T/NK cells. One patient mounted an extensive CD8 T-cell response directly after treatment, not accompanied with aggravating GVHD. Two patients showed nearly complete remission of GVHD, despite unresponsiveness to the extensive pretreatment. These findings justify further investigation of the IT combination for treatment of diseases mediated by T cells. (Blood. 2000;95:3693-3701)

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 010052944

Download citation: RISBibTeXText

PMID: 10845899


Related references

Suitability of a cocktail of CD34 and CD7 ricin A-immunotoxins for in vivo treatment of acute graft-versus-host-disease. Blood 90(10 Suppl. 1 Part 2): 376B, 1997

Phase I/II Trial of a Combination of Anti-CD3/CD7 Immunotoxins for Steroid-Refractory Acute Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation 25(4): 712-719, 2019

Ex-vivo treatment of donor bone marrow with anti-T-cell immunotoxins for prevention of graft-versus-host disease. Lancet 1(8375): 469-472, 1984

Graft-versus-host-disease (GVHD) prophylaxis using antibody-ricin immunotoxins for ex vivo treatment of donor marrow. Leukemia Research 10(1): 95-0, 1986

Toxicity and efficacy of anti-T-cell ricin toxin A chain immunotoxins in a murine model of established graft-versus-host disease induced across the major histocompatibility barrier. Blood 77(1): 182-194, 1991

Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin. JAMA 259(21): 3154-3157, 1988

Anti cd 2 t p 50 intact ricin immunotoxins for graft vs. host disease prophylaxis in allogeneic bone marrow transplantation. Leukemia Research 10(2): 145-154, 1986

Use of an anti-pan T-lymphocyte ricin a chain immunotoxin in steroid-resistant acute graft-versus-host disease. Blood 75(7): 1426-1432, 1990

Graft vs. host disease prophylaxis using antibody ricin immunotoxins for ex vivo treatment of donor marrow. Leukemia Research 10(1): 95, 1986

Combination treatment of bullous pemphigoid with anti-CD20 and anti-CD25 antibodies in a patient with chronic graft-versus-host disease. Bone Marrow Transplantation 30(5): 327-329, 2002

Ex vivo perfusion of intestinal allografts with anti-T cell monoclonal antibody/ricin A chain conjugates for the suppression of graft-versus-host disease. Transplantation 53(4): 717-722, 1992

Anti cd5 ricin a chain immunotoxin for prevention of acute graft versus host disease in closely hla matched unrelated donor bone marrow transplants. Experimental Hematology 18(6): 712, 1990

Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10). Blood 75(4): 1017-1023, 1990

Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis. British Journal of Haematology 113(1): 217-223, 2001

The in vivo anti-tumor activity of immunotoxins containing two versus one deglycosylated ricin A chains. Cancer Letters 98(1): 97-101, 1995