Effect of anti-CD4 monoclonal antibody combined with human CTLA4Ig on the survival of hamster liver and heart xenografts in Lewis rats.
We investigated the effects of pretransplant anti-CD4 monoclonal antibody (mAb) combined with human (h) CTLA4Ig on the survival of hamster heart and liver xenografts. Pretransplant anti-CD4 mAb (5 mg/kg x 4 days) or hCTLA4Ig (0.5 mg/rat on days 1, 3, and 5 after transplantation) treatment alone prolonged the survival of hamster liver xenografts in Lewis rats (mean survival time [MST]=10.5 days, n=6, and MST=9.0 days, n=5, respectively, compared with untreated Lewis recipients of hamster liver grafts, MST=6.0 days, n=6). The same regimen could not prevent hamster heart xenorejection. Pretransplant anti-CD4 mAb (5 mg/kg x 4 days) combined with hCTLA4Ig (0.5 mg/rat x 4) treatments increased survival of hamster liver xenograft fourfold (MST=24.2 days, n=5). The current results also show that IgG in the sera from Lewis recipients of hamster liver grafts treated with anti-CD4 mAb and hCTLA4Ig was threefold reduced at 6 days after transplantation compared with untreated Lewis rats. These results suggest a synergistic effect of anti-CD4 mAb combined with hCTLA4Ig in a liver xenograft transplantation model.
Yin
D P
DP
Department of General Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Sankary
H N
HN
Chong
A S
AS
Blinder
L
L
Ma
L L
LL
Williams
J W
JW
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D006224:Cricetinae; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D000069594:Abatacept