Methods of inducing immune tolerance using immunotoxins

US6103235A · kind A · utility

Assignees

• The United States of America, as represented by the Department of Health and Human Services · US
• THE UAB RESEARCH FOUNDATION · US

Inventors

• David M. Neville, Jr. · Bethesda, US
• Stuart Knechtle · Fitchburg, US

Key dates

• Filing date: Apr 15, 1997
• Grant date: Aug 15, 2000
• Expiry date: Apr 15, 2017

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2317/77
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Provided is a method of treating an immune system disorder not involving T cell proliferation, comprising administering to the animal an immunotoxin comprising a mutant diphtheria toxin moiety linked to an antibody moiety which routes by the anti-CD3 pathway, or derivatives thereof under conditions such that the disorder is treated. Thus, the present method can treat graft-versus-host disease. Also provided is a method of inhibiting a rejection response by inducing immune tolerance in a recipient to a foreign mammalian donor tissue or cells, comprising the steps of: a) exposing the recipient to an immunotoxin so as to reduce the recipients's peripheral blood T-cell lymphocyte population by at least 80%, wherein the immunotoxin is anti-CD3 antibody linked to a diphtheria protein toxin, wherein the protein has a binding site mutation; and b) transplanting the donor cells into the recipient, whereby a rejection response by the recipient to the donor organ cell is inhibited, and the host is tolerized to the donor cell.