Use of a non-depleting anti-CD4 antibody to modulate the immune response to coagulation factors VIII and IX.
The generation of antibodies to therapeutic factors VIII or IX is a major problem in the management of haemophilia and places potential limitations on the application of gene therapy. We have investigated the administration of a non-depleting anti-CD4 antibody for modulation of the immune response to human recombinant coagulation factors VIII and IX. In mice given these clotting factors, co-administration of anti-CD4 antibody significantly reduced the appearance of factor-specific antibodies. These data provide evidence that the neutralizing antibody response to exogenous coagulation factors may be controllable if non-depleting anti-CD4 antibody is co-administered at the time of initial replacement therapy.
Salooja
Nina
N
Haemostasis Research, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Kemball-Cook
Geoffrey
G
Tuddenham
Edward G D
EG
Dyson
Julian
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D015704:CD4 Antigens / Q000276:immunology*; D005164:Factor IX / Q000276:immunology*; D005169:Factor VIII / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D011994:Recombinant Proteins; D005169:Factor VIII; D005164:Factor IX