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[Analysis of cytolytic activity and cell surface phenotypes of lymphokine activated killer cells stimulated with R-IL 2 and an anti-CD 3 antibody].

We analyzed cytolytic activity and cell surface phenotypes of LAK (lymphokine activated killer) cells which were stimulated with recombinant IL-2 and an anti-CD3 antibody. This study involved 9 patients with astrocytomas, one patient with ganglioglioma, and one patient with medulloblastoma and their ages ranged between 5 and 80yr. Peripheral blood lymphocytes were separated from about 40 ml venous blood on a Ficoll-Paque gradient. After PBL's were cultured with r-IL 2 and anti-CD 3 antibody for about two weeks, more than 10(8) LAK cells could be obtained. Their cytolytic activity was measured by standard 4 hours-51Cr release assay and K 562, Daudi, U 251 MG, MCF-7, and autologous tumor cells were used as target cells. Their surface phenotypes (CD 3, CD 4, CD 8, CD 16, CD 25, Leu 7, HLA-DR) were measured by FACS. These LAK cells showed weaker killing activity against all kinds of tumor cells than usual LAK cells (LAK cells stimulated with r-IL 2 alone) did. Their surface phenotypes were more sensitive to CD 3 and less sensitive to CD 16 and Leu 7 than those of usual LAK cells. One of weak points of so-called LAK therapy is that many PBL's have to be obtained by leukapheresis and because of that, it is difficult to undertake LAK therapy to children or elderly patients. However, by using an anti-CD 3 antibody, enough LAK cells as effector of LAK therapy could be obtained more easily.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anti-CD3 monoclonal antibody induction therapy. Immunological equivalency with triple-drug therapy in heart transplantation.

This study examines the hypothesis that induction immunosuppressive therapy with murine anti-CD3 monoclonal antibodies (OKT3) reduces the frequency of rejection episodes in heart transplant recipients receiving 3-drug maintenance therapy with cyclosporine, azathioprine, and steroids. A group of 26 adult heart transplant recipients requiring preoperative intravenous inotropic drugs or with elevated serum creatinine received OKT3 induction as well as long-term triple drug therapy. Cyclosporine was withheld for the first 4 postoperative days allowing for resolution of cardiogenic renal dysfunction. A corresponding group of 26 heart transplant recipients received triple drug therapy alone started immediately before transplantation. Both groups were comparable in age, sex distribution, and follow-up period. The frequency of rejection episodes was identical for the two groups (0.003 episodes per patient month). Time to first rejection episode in the induction group, however, was delayed twofold as compared with the noninduction group (42 versus 21 days, p less than 0.01). Actuarial survival at 6, 12, and 18 months was 88%, 81%, and 81% for the induction group and 92%, 92%, and 87% for the noninduction group (p = NS). Treatment for rejection was not required in 35% of the induction group and 38% of the noninduction group (p = NS). OKT3 provides satisfactory immunosuppression in heart transplant recipients with hemodynamic or renal compromise, yet it does not reduce the frequency of rejection episodes compared with patients receiving triple drug therapy alone. Although the time to first rejection may be delayed, routine adjuvant use of OKT3 for induction in all heart transplant recipients may incur needless expense without providing an important immunological advantage as compared with triple drug immunosuppression alone.

Antibodies, Monoclonal↗

Cardiac allograft function with corticosteroid-free maintenance immunosuppression.

Potent prophylactic immunosuppressive protocols promote the safe withdrawal of corticosteroid maintenance. The benefits of corticosteroid-free maintenance immunosuppression include the absence of the cushingoid habitus, fewer infections, less obesity, and lower serum cholesterol. The incidence of allograft coronary artery disease is not increased by corticosteroid-free maintenance. To assess the long-term effects of corticosteroid-free immunosuppression on allograft function, we compared results of hemodynamic study and noninvasive evaluation over the 2-year follow-up of 57 patients on corticosteroid-free maintenance to 40 patients who required corticosteroid. Age and pretransplantation diagnoses were similar, but a greater percentage of those who required corticosteroid maintenance were female (28% versus 2%, p less than 0.001). Indexes of allograft function were similar in both groups and these indexes included ejection fraction, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, left ventricular end-diastolic dimension, and posterior wall thickness. Patient survival was identical in the two groups (98%). These data indicate that corticosteroids can be safely withdrawn with the subsequent early benefits and without compromising long-term allograft function.

Antibodies, Monoclonal↗

Unique antithymocyte serum versus OKT3 for induction immunotherapy after heart transplantation.

To determine the efficacy of a unique polyclonal rabbit antithymocyte serum (ATS), we compared 17 consecutive nonrandomized heart transplant recipients (mean age, 38 +/- 15 years) given a 7-day prophylactic postoperative course of locally produced ATS (whole serum, no Freund's adjuvant, IV) with 19 patients (mean age, 42 +/- 17 years) given 14 days of monoclonal antibody OKT3. Cyclosporine, steroid, and azathioprine dosages were similar. At 30 days the event-free incidence of rejection was 66% +/- 11% for OKT3 (2.3 events/100 patient-days) versus 47% +/- 12% for ATS (1.2 events/100 patient-days). At 60 days and thereafter, however, there was no difference in overall number of cumulative rejection episodes. Overall infection rates were similar in both groups: the ATS group tended to have more bacterial infections, whereas the OKT3 group displayed more viral infections. Antiidiotypic antibodies developed in 29% of the ATS group and in 22% of the OKT3 group. This report demonstrates the efficacy of this polyclonal serum preparation made without Freund's adjuvant when used as an adjunct for induction-prophylactic immunotherapy in heart transplant recipients when compared with OKT3.

Actuarial Analysis↗