Effect of pre-existing anti-diphtheria toxin antibodies on T cell depletion levels following diphtheria toxin-based recombinant anti-monkey CD3 immunotoxin treatment.

Abstract:

:Diphtheria toxin (DT)-based anti-CD3 immunotoxins have clinical relevance in numerous applications including autoimmune disease therapies and organ transplantation tolerance protocols. Pre-existing anti-DT antibodies acquired either by vaccination against diphtheria toxin or infections with C. diphtheriae may interfere or inhibit the function of these anti-CD3 immunotoxins. Previously, a full-length anti-rhesus monkey CD3 immunotoxin, FN18-CRM9, was shown to be less effective at depleting circulating T cells in animals with pre-existing anti-DT antibody titers than in animals without antibodies, and subsequent doses were ineffective. In this study, the T cell depletion function of a truncated DT based recombinant anti-monkey CD3 immunotoxin, A-dmDT390-scfbDb (C207), as part of a reduced intensity conditioning regimen prior to hematopoietic cell transplantation, was compared between two groups of monkeys: those with and without pre-existing anti-diphtheria titers. T cell depletion was comparable in both groups of monkeys, and therefore appeared to be unaffected by the presence of moderate levels of pre-existing anti-diphtheria antibodies.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

Matar AJ,Pathiraja V,Wang Z,Duran-Struuck R,Gusha A,Crepeau R,Tasaki M,Sachs DH,Huang CA

doi

10.1016/j.trim.2012.05.003

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

52-4

issue

1

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(12)00040-8

journal_volume

27

pub_type

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