Induction of an immune response through the idiotypic network with monoclonal anti-idiotype antibodies in the carcinoembryonic antigen system

Anti‐idiotype antibodies can mimic the conformational epitopes of the original antigent and act as antigent substitutes for vaccination and/or serological purposes. To investigate this possibility concerning the tumor marker carcinoembryonic antigent (CEA), BALB/c mice were immunized with the prevously described anti‐CEA monoclonal antibody (MAB) 5.D11 (AB1). After cell fusion, 15 stable cloned cell lines secreting anti‐lds (AB2) were obtained. Selected MAbs gave various degrees of inhibition (up to 100%) of the binding of 125I‐labeled CEA to MAb 5.D11. Abesence of reactivity of anti‐ld MAbs with normal mouse lgG was first demontrated by the fact that anti‐ld MAbs were not absorbed by passage through a mouse lgG column, and second because they bound specifically to non‐reduced MAb 5.D11 on Western blots. Anti‐5.D11 MAbs did not inhibit binding to CEA of MAb10.B9, another anti‐CEA antibody obtained in the same fusion as 5.D11, or that of several anti‐CEA MAbs reported in an international workshop, with the exception of two other anti‐CEA MAbs, bothe directed against the GOLD IV epitope. When applied to an ld‐anti‐ld competitive radioimmunoassay, a sensitivity of 2 ng/ml of CEA was obtained, which is sufficient for monitoring circulating CEA in carcinoma patients. To verify that the anti‐ld MAbs have the potential to be used as CEA vaccines, syngeneic BALB/c mice were immunized with these MAbs (AB2). Sera from immunized mice were demonstrated to contain AB3 antibodies recongnizing the original antigen, CEA, both in enzyme immunoassay and by immunoperoxidase staining of human colon carcinoma. These results open the perspective of vaccination against colorectal carcinoma through the use of anti‐idiotype antibodies as antigen substitutes. © 1992 Wiley‐Liss, Inc.