In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives

At immunolocalization of experimental tumors, idiotypic monoclonal antibodies, such as TS1 against cytokeratin 8, can be used to carry and deposit in vivo terapeutics in the tumor. These carriers also remain in the circulation and may cause negative side-effects in other tissues.In this report, several derivatives of the antiidiotypic antibody αTS1 were produced and tested for their clearing capacity of the idiotypic carrier antibody TS1. Intact monoclonal αTS1, scFv of a αTS1 and αTS1 Fab and Fab2′ fragments were produced by recombinant technology or by cleavage with Ficin. The scFv was tailored by use of the variable domain genes of the light and heavy chain from the hybridoma clone in combination with a (Gly4Ser)3-linker, followed by expression in E. coli  . When tested for clearing capacity, the intact divalent antiidiotypic IgG was found to be the most efficient. The divalent Fab2′ and the monovalent Fab fragment also demonstrated significant clearing, but lower than the intact antiidiotypic IgG. The αTS1 scFv antibody when injected separately was not found to clear the idiotype, but could do so when preincubated with the idiotype. Rapid excretion and in vivo instability of this low molecular weight antibody fragment may be the major reasons. Similar results were obtained when the system was reversed and the 131I-labeled antiidiotype IgG was cleared with the idiotype Fab2′ fragment.It is concluded that both intact antiidiotypic IgG, Fab2′ and Fab fragments are able to clear the idiotypic antibodies. The experimental data support the conclusion that the Fc parts from both the idiotype and the antiidiotype may contribute to this elimination.