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At least 307 records · Page 17Linked to original sources
PubMed1990

[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↗
PubMed1990

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↗
PubMed1990

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↗
PubMedDate not supplied

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↗
PubMed1990

The carbohydrate structures of a mouse monoclonal IgG antibody OKT3.

A mouse monoclonal antibody OKT3, of IgG2a isotype, was isolated from hybridoma culture fluid. Sugar analysis showed the presence of sialic acid, galactose, mannose, fucose, and N-acetylglucosamine, i.e. sugars typical for N-glycosidically linked carbohydrate chains. The absence of N-acetylgalactosamine revealed that O-glycosidically linked carbohydrates were not present. The purified antibody was reduced, alkylated, and separated into heavy and light chains, and all carbohydrates were shown to be associated with the heavy chains. The N-linked carbohydrate chains were isolated as alditols using strong alkaline-borohydride degradation and further fractionated on a concanavalin A-Sepharose column and high performance ion exchange chromatography with pulsed amperometric detection. Structural analysis was carried out on the isolated oligosaccharide alditols by chemical analyses, fast atom bombardment mass spectrometry, and 500-MHz 1H NMR spectroscopy. Triantennary and biantenary types of structures were found. The triantennary structures were present as trisialo and tetrasialo forms without fucose; the tetrasialo forms were shown to contain a sequence of Neu5Ac alpha 2-3Gal beta 1-3[Neu5Ac alpha 2-6]GlcNAc beta 1- on one of the branches. The biantennary structures were present as completely sialylated nonfucosylated species and as asialo-, agalacto-, and partially fucosylated structures.

Animals↗
PubMedDate not supplied

Therapy of refractory, recurrent heart rejection with multiple courses of OKT3.

The treatment for recurrent cardiac allograft rejection refractory to conventional immunotherapy is retransplantation. When retransplantation is not possible, alternative approaches must be undertaken. This report reviews the successful management of persistently recurring rejection using five serial 14-day courses of OKT3 in a 35-year-old man after two heart transplantations.

Adult↗
PubMedDate not supplied

Meningism in a ten-month-old infant during OKT3 therapy.

Organ transplantation has become widely applied as a therapy of end-stage organ dysfunction and is finding increasing application in the pediatric population. This has become possible largely through the use of improved immunosuppressive agents, such as OKT3. Aseptic meningitis associated with OKT3 has been previously reported, with a frequency rate of 3% to 14%, in adult renal allograft recipients. Aseptic meningitis after OKT3 therapy has not been reported in children. Meningitis, however, is a frequent infection encountered in young children, and the development of meningeal irritation during therapy with OKT3 may present a diagnostic dilemma. We describe aseptic meningitis in a 10-month-old infant after treatment of cardiac allograft rejection with OKT3.

Antibodies, Monoclonal↗
PubMed1990

Strategies of immunosuppression in cardiac transplantation.

Immunosuppression for cardiac transplantation, as currently practiced, is based to a large extent on clinical trials that can best be characterized as single-institutional, uncontrolled, or historically controlled studies. While these non-randomized, retrospective studies clearly advanced the science and art of cardiac transplantation to the point that survival rates approaching 90% at 1 year are achievable, the specific immunosuppressive protocols used at any given institution are likely based more on the individual transplant surgeon's or physician's training and experience, than on a firm scientific basis. Thus, a significant lack of uniformity exists among transplant centers in virtually all phases of immunosuppression. More clinical and basic research efforts are needed to unify immunosuppressive strategies following cardiac transplantation. In the future, greater individualization of therapy is likely to occur and more prospectively randomized, multi-center trials are likely to be carried out, particularly in the area of early rejection prophylaxis.

Antibodies, Monoclonal↗
PubMed1990

Effective induction immunosuppression for cadaver renal transplantation at the St. Francis Regional Medical Center.

The OKT3 induction protocol, when compared to a conventional drug protocol, resulted in an improvement in both short- and long-term patient and graft survival, especially in patients receiving a primary transplant. The 1-year allograft survival in primary transplants receiving OKT3 induction was 91% and the T1/2 of 13.5 years. This was accomplished while still being able to minimize the total drug dose of Aza, Pred, and CsA, thereby minimizing clinical complications. The use of OKT3 did not increase infections or malignant complications. This resultant significant improvement supports the passenger leukocyte theory of stimulation for allograft rejection. Further graft survival improvement in histodisparate allografts might be accomplished by OKT3 induction in concert with other methodologies that can control this cell type. The HLA antigens may not be as large an obstacle to grafting as previously suggested.

Antibodies, Monoclonal↗
PubMed1990

Renal transplantation at the Washington Hospital Center: experience with OKT3 and Minnesota antilymphoblast globulin for induction of immunosuppression.

These data demonstrate excellent long-term patient and graft survival rates when cytolytic induction therapy is combined with sequential addition of CsA. OKT3 and MAG produce virtually indistinguishable outcomes with low rates of rejection and DGF. The frequency of serious posttransplant complications, infection, rejection, and malignancy was low. Although both MAG and OKT3 are effective, each has its drawbacks. Problems associated with MAG therapy are leukopenia, thrombocytopenia, cumbersome administration, and difficulty monitoring the patient's specific level of induced immunosuppression. OKT3 is simpler to administer, easy to monitor, but first dose reactions may produce additional graft injury. Furthermore, OKT3 may not protect completely against all mechanisms of cellular rejection. In our patient population, the best results occurred when kidneys functioned immediately, when CsA was introduced promptly, and when there were several days of overlap, with MAG or OKT3, especially when OKT3 was used as the induction agent.

Adult↗