EXPRESSION AND CHARACTERIZATION OF A DIVALENT CHIMERIC ANTI-HUMAN CD3SINGLE-CHAIN ANTIBODY

Murine anti-CD3 monoclonal antibodies (MoAbs) are used in clinical pra ctice for immunosuppression. However, there are two major drawbacks to this treatment: the associated cytokine release syndrome and human an ti-mouse antibody response. To overcome these side-effects, the author s generated a chimeric anti-human CD3 single chain antibody, scUCHT1. It is an IgM variant of UCHT1, a mouse IgG1 MoAb directed against huma n CD3. scUCHT1 consists of the light and heavy variable chain binding domains of UCHT1 and a human IgM Fc region (CH2 to CH4), scUCHT1 was p roduced by COS-7 and SP2/0 transfectants, and mainly assembled in a di meric form. It retained the binding specificity and affinity of the pa rental MoAb UCHT1. In contrast to UCHT1, scUCHT1 did not induce T-cell proliferation and cytokine release (TNF-alpha and IFN-gamma) in in vi tro assays. These results suggest that the engineered chimeric anti-CD 3 single chain antibody (scUCHT1) may be useful in clinical immunosupp ressive treatment.