Therapeutic antibodies elicited by immunization against TNF-alpha.
Tumor necrosis factor-alpha (TNF-alpha) is critically involved in the pathogenesis of several chronic inflammatory diseases. Monoclonal antibodies against TNF-alpha are currently used for the treatment of rheumatoid arthritis and Crohn's disease. This report describes a simple and effective method for active immunization against self TNF-alpha. This vaccination approach leads to a T-cell-dependent polyclonal and sustainable anti-TNF-alpha autoantibody response that declines upon discontinuation of booster injections. The autoantibodies are elicited by injecting modified recombinant TNF-alpha molecules containing foreign immunodominant T-helper epitopes. In mice immunized with such molecules, the symptoms of experimental cachexia and type II collagen-induced arthritis are ameliorated. These results suggest that vaccination against TNF-alpha may be a useful approach for the treatment of rheumatoid arthritis and other chronic inflammatory diseases.
Dalum
I
I
M&E Biotech A/S, Hørsholm, Denmark.
Butler
D M
DM
Jensen
M R
MR
Hindersson
P
P
Steinaa
L
L
Waterston
A M
AM
Grell
S N
SN
Feldmann
M
M
Elsner
H I
HI
Mouritsen
S
S
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000628:therapy; D001323:Autoantibodies / Q000097:blood*; D002100:Cachexia / Q000276:immunology / Q000628:therapy; D003094:Collagen / Q000276:immunology; D000939:Epitopes; D007114:Immunization; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen