Idiotype switching of CD4-specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti-mouse IgG antibodies.
Immunotherapy using murine monoclonal antibodies (mAb) is limited by the host anti-mouse IgG response. Previous investigations demonstrated that a large proportion of the anti-mouse response was specific for idiotypic determinants of the mAb. This study demonstrates the feasibility of idiotype switching of therapeutic mAb to evade this anti-idiotype response. In this way prolongation of the therapeutic effectiveness of mAb treatment can be achieved. Using different CD4-specific mAb consecutively in rhesus monkeys it was possible to obtain therapeutic effectiveness in spite of host anti-mouse IgG antibodies, provided that no anti-idiotypic antibodies were present. Anti-constant part antibodies may even enhance therapeutic effectiveness.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D013045:Species Specificity
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes