Prolonged survival of nonhuman primate renal allograft recipients treated only with anti-CD4 monoclonal antibody.
The immunosuppressive efficacy of the monoclonal antibody OKT4A reactive with human and monkey CD4 cells was evaluated in cynomolgus renal allograft recipients. Low-dose (0.1 to 0.3 mg/kg/day) intact monoclonal antibodies (10 recipients) or F(ab')2 fragments (two recipients) were administered for 12 days. High-dose OKT4A (10 mg/kg) was administered on the day of transplantation as the only suppression in five animals. Four control animals received either no therapy or a monoclonal antibody nonreactive with monkey cells (OKT3). Maximum survival of the control animals and those treated with F(ab')2 was 11 days. Mean survival in the recipients of low-dose OKT4A was 25.4 +/- 4.3 days and in the group receiving high-dose OKT4A it was 39 +/- 6.4 days. All OKT4A-treated animals showed "coating" and CD4 modulation without depletion of circulating T cells. No modulation occurred in the F(ab')2-treated recipients. Serial allograft biopsy specimens showed reduced lymphocyte infiltration that was nearly complete in recipients of high-dose OKT4A. Biopsy-derived donor-reactive cytotoxic T-cell lines were generated regularly from recipients of low-dose, but not high-dose, OKT4A during periods of stable function. All animals treated with monoclonal antibodies developed an immunoglobulin G antimurine humoral response. Thus OKT4A is a potent immunosuppressive agent administered even as a single bolus, and depletion of CD4 cells is not required to suppress rejection. Anti-CD4 monoclonal antibodies may prove useful in patients, perhaps requiring only a limited number of higher-dose injections in the peritransplant period.
Cosimi
A B
AB
Transplantation Unit, Massachusetts General Hospital, Boston 02214.
Delmonico
F L
FL
Wright
J K
JK
Wee
S L
SL
Preffer
F I
FI
Jolliffe
L K
LK
Colvin
R B
RB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000917:Antibody Formation; D001706:Biopsy; D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006085:Graft Survival; D007165:Immunosuppression Therapy; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008252:Macaca fascicularis
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens