title: Chimeric monoclonal CD4 antibody--a novel immunosuppressant for clinical heart transplantation.
abstract: The murine CD4 monoclonal antibody (mAb) M-T412 effectively downregulates T-helper-inducer function, while exhibiting high affinity and specificity for an epitope formed by the V1 and V2 domain of CD4. The antibody was chimerized by combining the murine VH and VL parts to the constant region of a human IgG1 kappa immunoglobulin. This chimeric CD4 monoclonal antibody (chim CD4 mAb) cM-T412 was used for adjunct immunosuppression in addition to standard triple-drug therapy for patients after orthotopic (n = 10) and heterotopic (n = 1) heart transplantation (HTx). cM-T412 was administered intraoperatively and postoperatively on days 1-7, 9, 11, 13, 17, and 21. A control group of similar composition (10 orthotopic, 1 heterotopic HTx) was conventionally treated in an adjunct fashion with antithymocyte globulin (ATG) until cyclosporine (CsA) in serum had reached therapeutic levels. Over the total observation 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 control group, indicating a reduction of nearly 40%. Four of the 11 patients in the CD4 group have thus far not experienced any rejection crisis compared with two out of 11 in the control group. The mean time to the first rejection episode was 43.7 days in the CD4-treated patients versus 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. days) and had a better overall survival rate (91% vs. 73%) than control group pts. No anaphylactic reaction was observed. The only adverse event probably related to cM-T412 infusion was a transient decrease of blood pressure in one patient. Although this study has only a limited number of patients, addition of cM-T412 to standard triple drug therapy appears to be an effective, specific, and well tolerated adjunct to current immunosuppression that offers a new approach for an improved immunomodulatory regimen after heart transplantation.
authors.affiliation: Department of Cardiac Surgery, Ludwig-Maximilians University of Munich, Germany.
authors.forename: B M
authors.initials: BM
authors.lastname: Meiser
authors.forename: C
authors.initials: C
authors.lastname: Reiter
authors.forename: H
authors.initials: H
authors.lastname: Reichenspurner
authors.forename: P
authors.initials: P
authors.lastname: Uberfuhr
authors.forename: E
authors.initials: E
authors.lastname: Kreuzer
authors.forename: E P
authors.initials: EP
authors.lastname: Rieber
authors.forename: G
authors.initials: G
authors.lastname: Riethmüller
authors.forename: B
authors.initials: B
authors.lastname: Reichart
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins