Human antimurine antibodies

Muronomab-CD3 is a murine monoclonal antibody directed against the CD3 complex of the T-lymphocyte antigen receptor. This drug selectively diminishes the T-lymphocyte pool resulting in a strong lymphopenia. Similar to other nonhuman antibodies the generation of human antimurine antibodies (HAMA) limits its long-term use. 

In 1986, Muromonab CD-3 (OKT-3), which is a monoclonal antibody was first introduced to clinical practice, and the agent has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients. OKT-3 is administered only by intravenous injection and has a harmonic half-life of approximately 18 h. It binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration, CD-3-positive T lymphocytes are abruptly removed from the circulation. OKT-3 may be removed by opsonization by the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production [230]. 

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. ... 

Interference with diagnostic tests A patient who was given muromonab after renal allograft developed human antimurine heterophil antibodies, causing a falsely raised parathormone measurement [136 ]. 

Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan Jr AC. Human antimurine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 1985 45 879-885. 

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