Prolongation of primate cardiac allograft survival by treatment with ANTI-CD40 ligand (CD154) antibody.
BACKGROUND
We evaluated whether a humanized anti-CD154 antibody (hu5c8) prolongs primate cardiac allograft survival.


METHODS
Heterotopic cardiac allografts were performed between MHC class II-mismatched cynomolgus monkeys. Survival was compared between groups treated with a perioperative dosing of hu5c8 (group 1; n=6), sustained dosing with hu5c8 (group 2; n=3), and control regimens (n=4). All recipients received fresh donor-specific transfusions during surgery.


RESULTS
Median graft survival was 49 days (range 14 to 56) in group 1 and 106 days (range 56 to 245) in group 2, compared with 5 days (range 5 to 6) for controls (P<0.05 for all comparisons). Lymphocytic infiltrates were often present in hu5c8-treated grafts with stable contractility. Donor-specific mixed lymphocyte reaction was generally preserved. Vasculitis and cellular intimal proliferation were prevalent in rejected grafts but occurred later and were less prevalent in group 2.


CONCLUSIONS
Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 yielded improved survival and may be associated with a lower incidence of vascular pathology. We conclude that hu5c8 therapy is an effective approach for inhibiting acute cardiac allograft rejection in primates.
Pierson
R N
RN
Department of Cardiac and Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. robin.pierson@mcmail.vanderbilt.edu
Chang
A C
AC
Blum
M G
MG
Blair
K S
KS
Scott
M A
MA
Atkinson
J B
JB
Collins
B J
BJ
Zhang
J P
JP
Thomas
D W
DW
Burkly
L C
LC
Miller
G G
GG
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000235:genetics*; D023201:CD40 Ligand; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006321:Heart / Q000503:physiopathology; D016027:Heart Transplantation / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008252:Macaca fascicularis; D008562:Membrane Glycoproteins / Q000276:immunology*; D009200:Myocardial Contraction; D013997:Time Factors; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000473:pathology; D014657:Vasculitis / Q000473:pathology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D023201:CD40 Ligand