CHIMERIC MONOCLONAL CD4 ANTIBODY - A NOVEL IMMUNOSUPPRESSANT FOR CLINICAL HEART-TRANSPLANTATION

The murine CD4 monoclonal antibody (mAb) M-T412 effectively downregula tes T-helper-inducer function, while exhibiting high affinity and spec ificity for an epitope formed by the V-1 and V-2 domain of CD4. The an tibody was chimerized by combining the murine V-H and V-L parts to the constant region of a human IgG1 kappa immunoglobulin. This chimeric C D4 monoclonal antibody (chim CD4 mAb) cM-T412 was used for adjunct imm unosuppression in addition to standard triple-drug therapy for patient s after orthotopic (n=10) and heterotopic (n=1) heart transplantation (HTx). cM-T412 was administered intraoperatively and postoperatively o n days 1-7, 9, 11, 13, 17, and 21. A control group of similar composit ion (10 orthotopic, 1 heterotopic HTx) was conventionally treated in a n adjunct fashion with antithymocyte globulin (ATG) until cyclosporine (CsA) in serum had reached therapeutic levels. Over the total observa tion time (mean: 600 days), the number of acute rejection episodes per 100 patient days was 0.26 in the cM-T412 group versus 0.41 in the con trol group, indicating a reduction of nearly 40%. Four of the 11 patie nts in the CD4 group have thus far not experienced any rejection crisi s compared with two out of 11 in the control group. The mean time to t he first rejection episode was 43.7 days in the CD4-treated patients v ersus 25.3 days in the control group. In addition the interval to the second rejection episode was longer in CD4 patients than in controls. Furthermore, patients treated with chim CD4 mAb had fewer episodes of infection during the first year after HTx (0.49 vs. 0.91 per 100 pt. d ays) and had a better overall survival rate (91% vs. 73%) than control group pts. No anaphylactic reaction was observed. The only adverse ev ent probably related to cM-T412 infusion was a transient decrease of b lood pressure in one patient. Although this study has only a limited n umber of patients, addition of cM-T412 to standard triple drug therapy appears to be an effective, specific, and well tolerated adjunct to c urrent immunosuppression that offers a new approach for an improved im munomodulatory regimen after heart transplantation.