Sideeffects

ALS is administered via a central nervous catheter to avoid irritation following intramuscular or ordinary intravenous injection. Many side-effects seen after administration of polyclonal or monoclonal antibodies against lymphocytes are probably due to antibodies cross-reacting with other tissues. A common problem is serum sickness (fever, malaise, dyspnea, hypotension, edema, cutaneous eruptions, lympha-denopathy, arthralgia and headache). Histologically there may be signs of vasculitis. Many of these symptoms seem to be associated with occurrence of immune complexes. Monoclonal antibodies also have side-effects, even in their humanized forms. The first few injections of anti-CD3 often cause fever, gastrointestinal and respiratory disturbances, headache and anorexia, symptoms sometimes referred to as 'the first-dose syndrome'. The side-effects caused by both ALS and anti-CD3 are thought to be mediated by release of tumor necrosis factor (TNF), interferon y (IFNy) and possibly interleukin 2 (1L-2). Transient renal dysfunction attributed to cytokine-induced renal capillary leakage, has also been reported. Other T cell-specific mAbs do not cause

Figure 1 Measurement of a human antimouse antibody response to therapeutic Mabs. An antimouse antibody is first bound to a surface (A). The therapeutic mouse Mab is then added, together with the human serum to be examined (1; B, C). Lastly, an antihuman Ig antibody is added (2; D). The binding of this last antibody is dependent on the presence of antimouse antibodies in the patient's serum.

Figure 1 Measurement of a human antimouse antibody response to therapeutic Mabs. An antimouse antibody is first bound to a surface (A). The therapeutic mouse Mab is then added, together with the human serum to be examined (1; B, C). Lastly, an antihuman Ig antibody is added (2; D). The binding of this last antibody is dependent on the presence of antimouse antibodies in the patient's serum.

cytokine release and do not result in so many side-effects. More rarely, symptoms from the central nervous system may occur. There is a risk of lympho-proliferative conditions with both ALS and OKT3, at least after extended use. It has been suggested that side-effects of ALS may be minimal with a remaining therapeutic effect if the administration of ALS is adjusted according to the daily level of T lymphocytes in the blood. Of course, the immunosuppressive effects of both polyclonal and monoclonal lymphocyte-specific antibodies are associated with a risk of opportunistic infections.

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