Therapy in kidney transplant rejection using murine monoclonal IgG2a A1CD3 (Cedetrin)

BACKGROUND: One of the substances used in recent years to suppress immune reactions after organ and tissue transplantations is mouse IgG2a globulin which acts selectively on CD3 lymphocytes; it is known under the name of Orthoclone (Ortho Co.) An analogous preparation was developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, although the idiotype is different. The authors submit a report on the experience with treatment of rejection of transplanted kidneys. METHODS RESULTS: Monoclonal mouse globulin IgG2a (Cedetrin) was administered to 20 patients after renal transplantation on account of a rejection episode or progressing rejection; the mean interval after transplantation was 16.1 (range 0.25-96) months; the rejection episode or progressing rejection responded little in the majority of patients to 6-alpha-methyl prednisolone (Urbason, Hoechst, Solu-Medrol, Upjohn). For prophylactic immunosuppression the following combinations were used: cyclosporin + azathioprine + prednisone (17x) or azathioprine + prednisone (3x). Cedetrin was administered by the i.v. route in two to 11 doses a 3 mg substance. Of 20 patients in 6 Cedetrin administration had to be discontinued (allergy, infection, leucopenia, hyperhydration). In 14 the tolerance was satisfactory, the type and frequency of side-effects was similar as after Orthoclone; the antibody formation was less frequent. The specificity of Cedetrin as regards its action on T lymphocytes was confirmed. The effect was good to very good in 6 of 8 patients where the rejection filtrate was histologically active. In 9 patients treated during the first year after renal transplantation the cumulative survival of the graft at the end of the 12th, 24th and 36th month following transplantation was 89%, 67% and 56% resp. Because the therapeutic effect depended on histologically proved rejection activity, the authors consider biopsy of the graft before Cedetrin treatment essential. CONCLUSIONS: The therapeutic administration of monoclonal mouse globulin IgG2a A1CD3 (Cedetrin), developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, produced by Exbio Co., CR) has a favourable effect on rejection episodes or progressing rejection of transplanted kidneys. Treatment is indicated in confirmed histologically active rejection.