Therapeutic Use of OKT3 Monoclonal Antibody for Acute Renal Allograft Rejection

Abstract

OKT3, a murine monoclonal anti-T-cell antibody, was used to treat acute renal allograft rejection crises in 140 patients. When used for primary treatment of initial rejections, it was effective in all 20 recipients of related-donor (RD) grafts and in 70 of 74 recipients of cadaver-donor (CD) grafts. OKT3 was also used for resistant rejection unresponsive to conventional antirejection drugs and was effective in 11 of 13 RD and in 26 of 33 CD recipients. Rerejection occurred in 58% of patients in the OKT3 primary treatment group and in 35% of patients in the OKT3 rescue group. Fifty-nine percent of the patients produced anti-OKT3 antibodies. Nearly all recipients experienced a flu-like syndrome following the first and second daily doses of OKT3. Two-year actuarial patient survivals were 100 and 96% for RD and CD recipients, respectively. In the OKT3 primary treatment group, two-year actuarial RD and CD graft survivals were 91 and 76%, respectively. In the OKT3 rescue group, the two-year actuarial RD and CD graft survivals were 85 and 55%, respectively. A proposed immunosuppressive effect of OKT3 is T-cell inactivation by blocking antigen receptors linked to OKT3-reactive molecules. Reuse of OKT3 for recurrent rejection or subsequent organs may be hampered by anti-OKT3 antibody production. OKT3 is an effective steroid-sparing treatment for renal allograft rejection.

Predicting Factors of Long-Term Results of OKT3 Therapy for Steroid Resistant Acute Rejection following Cadaveric Renal Transplantation

“…Long-term graft survival is not often addressed after OKT3 rescue therapy, and when it is, is usually assessed less than 24 months after treatment, showing rates of graft survival ranging from 50% to 87% [4, 8, 10-12, 14, 18]. These latter studies emphasized that the graft survival was influenced by (a) the nature of the graft (cadaveric vs. living related donor) [18]; (b) the components of the AR, i.e., the presence or absence of either vascular lesions or chronic lesions [12,13]; (c) the CsA trough levels at the beginning of OKT3 therapy [6]; (d) time between initiation of OKT3 therapy and the initial diagnosis of AR [6,8]. Another factor that might influence short-term graft survival following OKT3 as rescue therapy is the concomitant administration of CsA: CsA is usually withheld during OKT3 therapy and resumed 2 to 3 days before its end to reduce the risk of CsA nephrotoxicity and over-immunosuppression [3,5,6,10,11,18].…”

“…These latter studies emphasized that the graft survival was influenced by (a) the nature of the graft (cadaveric vs. living related donor) [18]; (b) the components of the AR, i.e., the presence or absence of either vascular lesions or chronic lesions [12,13]; (c) the CsA trough levels at the beginning of OKT3 therapy [6]; (d) time between initiation of OKT3 therapy and the initial diagnosis of AR [6,8]. Another factor that might influence short-term graft survival following OKT3 as rescue therapy is the concomitant administration of CsA: CsA is usually withheld during OKT3 therapy and resumed 2 to 3 days before its end to reduce the risk of CsA nephrotoxicity and over-immunosuppression [3,5,6,10,11,18]. In some cases, CsA is not discontinued during OKT3 therapy but the dosage is halved, and one study showed that continuing treatment with low doses of CsA while administering OKT3 for steroid-resistant AR may have some beneficial effects on the reversal of rejection [19].…”

Therapeutic Targets for the Prevention of Type 1 Diabetes Mellitus

“…OKT-3 has been used to treat acute rejection in solid organ transplants, and clinical studies demonstrated it's efficacy in reversing allograft rejection in patients undergoing renal, liver, and cardiac transplantation [60][61][62][63][64]. Response failures were attributed to inadequate doses of OKT-3, human antimouse antibodies directed at the drug, and rapid removal of the immunoglobulin from circulation [59,[65][66].…”

Abstracts 146–159

“…This together with downregulation of proximal tubule Na transporters [53] is likely to play a significant role in the reduced urinary concentration. Ischemia-induced acute renal failure, aging and water loading of rats (Table 2) has been shown to be associated with dysregulation of aquaporins as well [19,54,55].…”

“…Its use, however, is complicated by an increased risk of infections and malignancies. Moreover, a failure to prevent recurrent rejections effectively has also been observed after first-line rejection treatment with OKT3 [55].…”