Related Experiment Videos
[Immunosuppression, ongoing clinical trials]
1CHU de Rennes.
MONOCLONAL ANTIBODIES: Monoclonal antibodies have been humanized to improve their duration of action and their tolerance. Lymphocyte-depleting humanized anti-CD3 antibodies are globally well tolerated. Coupled with an immunotoxin, Campath 1H, a humanized anti-CD3 antibody with specific anti-CD52 depleting properties which also depletes immunocompetent cells, is being tested. There is increasing interest in the use of monoclonal antibodies in combination with rapamycin. SIROLIMUS AND EVEROLIMUS: The half-life of sirolimus is twice that of everolimus. Otherwise quite similar, these compounds have dose-dependent side effects: leukopenia, thrombocytopenia, hyperlipidemia. There use allows a lower dosage for the calcineurin inhibitor. Sirolimus is particularly active in reducing intimal proliferation within the vessel walls. Precise indications at the present time include induction of tolerance, withdrawal of the calcineurin inhibitor, use of low-dose calcineurin inhibitor, and corticosteroid withdrawal. ELIMINATING THE SIDE EFFECTS OF CORTICOSTEROIDS: Complications resulting from the use of corticosteroids, particularly bone complications, are still a problem with the low doses used in long-term regimens for transplant recipients. Several means have been proposed to reduce the risk. Total withdrawal is possible, but the risk of an increased rate of acute rejection limits indications. It appears that total withdrawal then complete abstention is not compatible immunologically. IMMUNOSUPPRESSORS IN PERSPECTIVE: Three groups of compounds have immunosuppressor potential: anti-adhesion molecule antibodies, co-stimulation blockers, and molecules inhibiting T-lymphocyte activators and their signalization factors.
MONOCLONAL ANTIBODIES: Monoclonal antibodies have been humanized to improve their duration of action and their tolerance. Lymphocyte-depleting humanized anti-CD3 antibodies are globally well tolerated. Coupled with an immunotoxin, Campath 1H, a humanized anti-CD3 antibody with specific anti-CD52 depleting properties which also depletes immunocompetent cells, is being tested. There is increasing interest in the use of monoclonal antibodies in combination with rapamycin. SIROLIMUS AND EVEROLIMUS: The half-life of sirolimus is twice that of everolimus. Otherwise quite similar, these compounds have dose-dependent side effects: leukopenia, thrombocytopenia, hyperlipidemia. There use allows a lower dosage for the calcineurin inhibitor. Sirolimus is particularly active in reducing intimal proliferation within the vessel walls. Precise indications at the present time include induction of tolerance, withdrawal of the calcineurin inhibitor, use of low-dose calcineurin inhibitor, and corticosteroid withdrawal. ELIMINATING THE SIDE EFFECTS OF CORTICOSTEROIDS: Complications resulting from the use of corticosteroids, particularly bone complications, are still a problem with the low doses used in long-term regimens for transplant recipients. Several means have been proposed to reduce the risk. Total withdrawal is possible, but the risk of an increased rate of acute rejection limits indications. It appears that total withdrawal then complete abstention is not compatible immunologically. IMMUNOSUPPRESSORS IN PERSPECTIVE: Three groups of compounds have immunosuppressor potential: anti-adhesion molecule antibodies, co-stimulation blockers, and molecules inhibiting T-lymphocyte activators and their signalization factors.