Consumption of monoclonal anti-idiotypic antibody by neoplastic B lymphocytes: A guide for immunotherapy

Abstract

A quantitative analysis in vitro of events which might occur on administration of mouse monoclonal anti-idiotypic antibody to a recipient with a B cell neoplasm has been made. The L2C leukaemic cells of guinea pigs, which closely resemble those of human lymphoma in expression and metabolism of immunoglobulin have been used as a model. Exposure of neoplastic B cells to antibody results in rapid binding of approximately 420,000 molecules of antibody per cell at saturation, and the amount consumed does not increase markedly over the next 4 h of exposure at 37 degrees C. This is in spite of the fact that secretion of idiotypic IgM continues unaffected by the presence of antibody, and reflects the fact that the amount of IgM secreted during this period is low compared to the amount displayed on the cell surface. If cells undergo lysis, however, the antibody consumed is approximately doubled: thus a recipient with an estimated tumour load of 10(12) cells would require 200 mg of monoclonal anti-idiotype for binding to surface and intracellular antigen. The effect of the soluble idiotypic IgM found in serum on the ability of antibody to bind target cells has been examined by means of the fluorescence activated cell sorter. Access of antibody to the cells is efficiently blocked by competing idiotypic IgM in the fluid phase, with no indication of preferential binding to cell surface idiotype. Immunotherapeutic doses should be designed therefore to overcome this additional antigenic load in secreting tumours, which form the majority of B cell neoplasms.