Antilymphocyte antibodies

The improved short-term outcomes gained from induction therapy come with a degree of risk. By using these highly immunosuppressive agents, particularly the antilymphocyte antibodies (ALAs), muronomab-CD3 (OKT-3), and the antithymocyte antibodies, the body loses much of its innate ability to mount a cell-mediated immune response, which increases the risk of opportunistic infections and cancer.7,10... 

Antilymphocyte antibody acts primarily on the small, long-lived peripheral lymphocytes that circulate between the blood and lymph. With continued administration, "thymus-dependent" lymphocytes from lymphoid follicles are also depleted, as they normally participate in the recirculating pool. As a result of the destruction or inactivation of T cells, an impairment of delayed hypersensitivity and cellular immunity occurs while humoral antibody formation remains relatively intact. ALG and ATG are useful for suppressing certain major compartments (ie, T cells) of the immune system and play a definite role in the management of solid organ and bone marrow transplantation. 

Woodruff, M.F.A., Reid, B., James, K. (1967). Effect of antilymphocytic antibody and antibody fragments on human lymphocytes in vitro. Nature 215, 591-594. 

The antilymphocyte globulin is obtained through the immunization of horses with human lymphoid cells or with fetal thymus cells. The antilymphocyte antibody destroys the T cells and impairs delayed hypersensitivity and cellular immunity without altering humoral antibody formation. The pattern of immunosuppression obtained with antilymphocyte globulin is identical to that brought about following thoracic duct drainage that depletes the numbers of small lymphocytes. 

In development the same types of major questions always remain to be answered in appropriate preclinical studies, even if the nature of those experiments has changed as greater understanding and more searching techniques have enabled more precise or more specific questions to be asked. This generalization can be illustrated by the history of the industrial production of interferon and antilymphocyte antibody. 

The common features of graft-versus-host disease are severe itching and persistent diarrhea. Treatment with prednisolone and, if necessary, antilymphocyte antibodies, and/or ciclosporin can help. Hepatic involvement can be mild but can progress to liver failure in spite of optimal treatment (102). Oral comphcations may be related to graft-versus-host disease but can also result from intensive chemotherapy/irradiation or intensive antibiotic treatment (103). 

Hale G et al. Removal of T cells from bone marrow for transplantation a monoclonal antilymphocyte antibody that fixes human complement. Blood 1983 62 873-882. 

The manufacturers of basiliximab say that patients in phase 3 studies received basiliximab with muromonab-CD3 for episodes of rejection, with no increase in adverse events or infections. Human antimurine antibody responses were reported in 2 of 138 patients receiving basiliximab and 4 of 34 patients receiving both basiliximab and muromonab-CD3. Therefore, the manufacturers say that if basiliximab has been given, muromon-ab-CD3 or other murine antilymphocytic antibody preparations can still subsequently be given. ... 

However, in one clinical study in heart transplant patients taking ciclosporin, mycophenolate, and corticosteroids, use of daclizumab with another antilymphocyte (such as mnromonab-CD3 or antithymocyte immunoglobniin) appeared to be associated with a higher incidence of fatal infection 8 of 40 patients died, compared with 2 of 37 who received an antilymphocyte and placebo. The manufacturer suggests that concurrent use of daclizumab with another antilymphocyte antibody in patients receiving intensive immunosuppression may be a factor leading to fatal infection. Caution may be warranted, and more study is needed. 

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