Suppression of antibody responses in rats to murine anti-CD4 monoclonal antibodies by conjugates with monomethoxypolyethylene glycol

The effectiveness of therapeutically relevant xenogeneic monoclonal antibodies (MoAb) may be counteracted by their inherent immunogenicity. Since conjugates of diverse proteins with monomethoxypolyethylene glycol (mPEG) were shown to induce Ag-specific tolerance in mice and rats, we used outbred rats in this study as an experimental model for establishing the tolerogenicity of mPEG conjugates of murine MoAb. The results demonstrate that: (i) murine anti-rat CD4 MoAb (W3/25) were more immunogenic than murine anti-human CD4 MoAb (MAX.16H5) in rats; (ii) W3/25 preferentially induced an anti-idiotypic (anti-id) antibody response; and (iii) antibodies to both common and idiotypic determinants could be suppressed in rats by treatment with W3/25(mPEG) 28.