Antibodies to Shared Idiotypes as Agents for Analysis and Therapy for Human B Cell Tumors

Monoclonal anti-idiotypic antibodies generated against idiotypic immunoglobulin (lg) of neoplastic B lymphocytes can be selected from growing hybridoma clones by their ability to recognize idiotypic but not normal lgM. This group of antibodies can be subdivided into those that bind to the target tumor cells in the presence of normal human serum (~85% of the clones) and those in which binding is inhibited by serum (~15%). The former appear to be specific for private idiotypic determinants whereas the latter recognize cross-reacting idiotypic determinants. Such cross-reactivity is reflected both in recognition of a small percentage of normal Ig and also in binding to other lymphomas. The anti-idiotypes specific for private determinants can be used for therapy, with only idiotypic Ig secreted by tumor cells able to block its access to cells. The cross-reacting anti-idiotypes will face in addition the barrier of the proportion of normal lg with which it reacts. The attraction of using a single monoclonal reagent for more than one patient has led us to develop an assay that measures the level of such blocking and to propose that those recognizing