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Monitoring Stem Cell Research 
rejection. While this association has not been reported by other 
centers using OKT3 prophylaxis, it is believed that the development 
of immune-complex disease, inadequate immunosuppression due to 
decreased OKT3 levels or that OKT3 sensitization may be a marker 
for patients at higher risk for humoral rejection may be responsible 
for this phenomenon. 
Interleukin-2 Receptor Inhibition 
A new class of drugs has been developed which targets the high 
affinity IL-2 receptor. This receptor is present on nearly all activated 
T cells but not on resting T cells. In vivo activation of the high-affinity 
IL-2 receptor by IL-2 promoted the clonal expansion of the activated 
T cell population. A variety of rodent monoclonal antibodies directed 
against the a chain of the receptor have been used in animals and 
humans to achieve selective immunosuppression by targeting only T- 
cell clones responding to the allograft. Chimerisation or 
humanisation of these monoclonal antibodies resulted in antibodies 
with a predominantly human framework that retained the antigen 
specificity of the original rodent monoclonal antibodies. A fully 
humanized anti-IL2R monoclonal antibody, daclizumab, and a 
chimeric anti-IL-2R monoclonal antibody, basilbdmab, have 
undergone successful phase III trials demonstrating their efficacy in 
the immunoprophylaxis of patients undergoing renal and cardiac 
transplantation. 
Both agents have immunomodulatory effects that are similar to 
those of other monoclonal antibody-based therapies (i.e., induction of 
clonal anergy rather than clonal deletion). The advantages of these 
agents include their lack of immunogenicity, long half-lives, ability to 
repeat dosing, and short-term safety profile. Daclizumab appears to 
be an effective adjuvant immunomodulating agent in cardiac 
allograft recipients. It has advantages over conventional induction 
therapy as it is more selective and can be used for prolonged and 
potentially repeated periods. Studies v\hth larger cohorts are needed 
to further study the short-term and long-term survival benefits for 
patients following organ transplantation and should determine the 
optimal dosing schedules of these new agents. 
4. STEM CELL TRANSPLANTATION AND IMMUNO-SUPPRESSION 
Matemo-Fetal Tolerance 
As outlined above, when tissues from an HLA-disparate donor are 
transplanted into a recipient they are always recognized as foreign. 
PRE -PUBLICATION VERSION 
