Effect of pre-existing anti-diphtheria toxin antibodies on T cell depletion levels following diphtheria toxin-based recombinant anti-monkey CD3 immunotoxin treatment.
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.
Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA, United States.
Abraham J
AJ
Matar
Vimukthi
V
Pathiraja
Zhirui
Z
Wang
Raimon
R
Duran-Struuck
Ashley
A
Gusha
Rebecca
R
Crepeau
Masayuki
M
Tasaki
David H
DH
Sachs
Christene A
CA
Huang
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D004167:Diphtheria Toxin / Q000276:immunology* / Q000494:pharmacology; D000922:Immunotoxins / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D008251:Macaca; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014180:Transplantation; D019172:Transplantation Conditioning; D014181:Transplantation Immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004167:Diphtheria Toxin; C114317:FN18-CRM9; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins