Antigenic Modulation as a Limiting Factor in the Treatment of B-Cell Lymphoma with Anti-Idiotype Antibody
In exploring antibody (Ab) approaches to the treatment of malignant disease, one major problem is antigenic modulation, which allows tumour cells confronted by Ab to avoid damage from effector systems such as complement through redistribution and internalization of immune complexes. Working with anti-idiotype (anti-Id) Ab directed against neoplastic B lymphocytes we describe how Ab derivatives which are univalent but retain an intact Fc region can avoid this problem. Progress in this work has led to the construction of chimaeric molecules in which univalent Fab’γ from Ab is linked by thioether bonds to normal immunoglobulin (Ig) of the species to undergo immunotherapy. Two such derivatives, FabIgG and FabFc which use IgG and Fcy respectively as effector partners of the Ab Fab’γ, appear superior to parent Ab in their ability to invoke complement and K cell killing of target lymphocytes. They also show promise of utilizing Fab’γ from any source including monoclonal reagents and, because they present homologous Ig, should prove minimally immunogenic and efficient recruiters of host effector systems.
KeywordsThioether Bond Univalent Derivative Peptic Digestion Antigenic Modulation Lymphoma Therapy
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