Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the a-chain of the human interleukin-2 receptor

摘要

The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number ofthem. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesizedtwo anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbsare produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of humancomplement, the individual Abs are negative; however, when used in combination, complement activation was performed.When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not displaythis property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, bycombination of an anti-CD4 mAb with one directed against the a-chain of the human IL2 receptor, nearly 100% inhibitionof the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4mAb and an anti-IL2Rcc chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicatingthat this mAb cocktail could be a new strategy for immunosuppressive therapy.