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PubMed1989

OKT3-associated adverse reactions: mechanistic basis and therapeutic options.

OKT3, a prototypic monoclonal antibody directed at the lineage-specific CD3 antigen expressed on mature T cells, is an effective immunosuppressant in organ graft recipients. Unfortunately, a variety of adverse reactions are observed following the first and second doses of OKT3. In a series of experiments designed to examine the signaling repertoire of OKT3, it was found that (1) OKT3 is an effective substitute for the alloantigen stimulus in the activation of antigen-specific memory T cells; (2) OKT3 is a potent inducer of cytolytic activity (secondary cytotoxic T-cell activity as well as natural killer-cell activity); (3) OKT3 is also an inducer of interleukin-2 and interferon gamma production; and (4) of the immunosuppressants currently in clinical use, cyclosporine greater than methylprednisolone greater than 6-mercaptopurine (an in vivo cleavage product of azathioprine) in curtailing T-cell activation with OKT3. Collectively, these observations suggest a potential mechanistic basis for the adverse reactions associated with OKT3 and provide experimental support for therapeutic strategies that include the use of cyclosporine and/or methylprednisolone before OKT3 administration.

Antibodies, Monoclonal↗
PubMed1987

[Preventive treatment of rejection by the prolonged administration of OKT3: decrease of the immune response of the host].

Clinical use of OKT3 for the treatment of ongoing rejection episodes has already been demonstrated as being highly effective. This work shows for the first time that combining azathioprine and OKT3 was able to delay as well as to decrease both the intensity and the quality of the anti-OKT3 immunization, allowing a 1-month prophylactic use of the MoAb. It also proves that OKT3 used prophylactically during one month can lead to 4-year first cadaver graft and patient survival rates better than those ever reported with any other immunosuppressive regimen. These results were obtained with lower doses of steroids and other immunosuppressive agents than in conventionally treated control patients. After the first two injections of OKT3, tolerance was perfect allowing out-hospital administration, and side effects consisted only in an increased number of viral infections instead of the bacterial infections observed in the conventional treatment groups. The prophylactic use of OKT3 should give even better results if it were possible to reach a 1-month administration schedule in all patients by modulating the dose of OKT3 according to the T3+ cell count and the monitoring of serum OKT3 levels.

Antibodies, Monoclonal↗
PubMed1987

[Immunologic surveillance of liver transplant patients using monoclonal antibodies against lymphocyte subpopulations].

A precise immunological surveillance of liver graft recipients can allow the adaptation to each patient of an adequate immuno-suppressive treatment. In 11 liver-transplanted patients (7 primitive biliary cirrhoses, 2 post-hepatic cirrhoses, one bile duct atresia with one antitrypsin deficit) different lymphocyte subpopulations were tested before transplantation and at days 3, 5, 7, 15, 30, 60 and 120 after grafting using OKT3, OKT4, OKT8 (Orthoclone, France). In 6 patients presenting one or more rejections, the (T4+):(T8+) lymphocyte ratio was significantly increased during the days preceding rejection. In all cases, the (T4+):(T8+) ratio increase was linked to a (T4+) helper lymphocyte augmentation. In the 6 patients who did not present any rejection, the (T4+):(T8+) ratio did not increase at long term. A decrease of the (T4+):(T8+) ratio, along with an augmentation of (T8+) lymphocytes, was noticed at long term in patients free of chronic rejection. The evolution of T lymphocyte populations, followed using monoclonal antibodies and mainly the (T4+):(T8+) ratio, can provide a test for rejection predictability of for the prognosis of tolerance to liver allografts.

Antibodies, Monoclonal↗
PubMed1988

Nosocomial aseptic meningitis associated with administration of OKT3.

An outbreak of nosocomial aseptic meningitis involving four renal allograft recipients on the transplant service occurred in July 1986, shortly after the release of the murine monoclonal antibody OKT3 for therapy for acute allograft rejection. No bacteria, fungi, or viruses were isolated from cultures of the cerebrospinal fluid of the four patients. All four had acute allograft rejection treated with OKT3 and developed signs and/or symptoms of meningitis within 72 hours of receiving the drug. To identify potential risk factors, the four patients with aseptic meningitis were compared with 12 patients on the renal transplant service in July 1986 who did not have signs or symptoms of meningitis. The development of aseptic meningitis was strongly associated with administration of OKT3. Because of this association, prospective surveillance of meningitis in patients receiving OKT3 was instituted. From November 1986 to May 1987, three (14%) of 21 patients treated with OKT3 developed aseptic meningitis. The clinical course of aseptic meningitis associated with OKT3 appears to be benign and self-limited. Nonetheless, this observation warrants continued surveillance of OKT3 therapy.

Antibodies, Monoclonal↗
PubMed1988

Neurologic complications of immunosuppressive agents.

The immunosuppressive agents that are an integral part of organ transplantation serve to protect grafts from rejection as well as to prevent or treat GVHD. They include CsA, corticosteroids, OKT3 monoclonal antibody, HDARA-C, azathioprine, and ATG. Of these, all but azathioprine and ATG have direct neurologic complications that are due to the drugs themselves and not just excessive immune suppression. With increasing success in solid organ and bone marrow transplantation and increasing patient survival, one can expect to see more patients who suffer neurologic toxicity.

Adrenal Cortex Hormones↗