OKT3 is the first anti-CD3
monoclonal antibody available for treatment in humans. Over the last few years it has proven to be a very powerful
immunosuppressive agent in
renal transplantation. Clinical studies have shown that
OKT3 is superior to high-dose
steroids as first-line treatment for acute renal allograft rejection. Furthermore, it is comparable to
antithymocyte globulin (ATG) in treating
steroid-resistant rejection and is also effective as rescue treatment in ATG- and
antilymphocyte globulin-(ALG-) resistant rejection. Despite its excellent rejection-reversal rate,
OKT3 treatment is followed by a substantial percentage of re-rejections, most of which respond well to
steroids. In the early post-
transplantation period, a prophylactic course of
OKT3 is very effective in preventing acute rejections, and in this respect it is probably equivalent to ATG. Indirect evidence exists that a prophylactic course of
OKT3 may be beneficial in immunologically high-risk patients and in patients with
delayed graft function. However, more clinical studies are required to answer the question whether
OKT3 should be given as induction treatment, as first-line treatment, or as rescue treatment. To answer this question, the side effects of
OKT3 should also be taken into account. First-dose-related side effects, although frequent and disturbing, are usually transient and seldom life-threatening, provided
overhydration has been corrected and
steroids have been given before the first administration. These side effects are attributed to the release of
cytokines as a result of T-cell activation or lysis. After exposure of patients to
OKT3 an increased incidence of
infections and
malignancies has been reported. However, it is not yet clear whether this is due to
OKT3 as such, or whether it merely reflects the total burden of immunosuppression. Xeno-sensitization represents an important limitation to
OKT3 treatment, although a second or third course can still be effective in patients with low antibody titers. The precise immunosuppressive mechanism of anti-CD3
monoclonal antibodies is yet unknown. Monitoring of patients treated with
OKT3 revealed CD3 and/or
T-cell antigen receptor depletion and immunological incompetence of remaining T cells. More clinical data are required to establish the correct dose and duration of
OKT3 treatment. In conclusion,
OKT3 is a powerful
immunosuppressive agent but its real value in
renal transplantation remains to be determined. A practical approach may be to reserve it for the treatment of
steroid-resistant rejections.(ABSTRACT TRUNCATED AT 400 WORDS)