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Inhibition of in Vivo Growth of Murine Plasmacytoma MOPC-460 by Monoclonal Anti-Idiotypic Antibodies Directed at Distinct Idiotypes of the Immunoglobulin on the Surface of MOPC-460¹

Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Naples, Italy [S. H. B., C. G.], and the Unite d'Immunochimie Analytique, Institute Pasteur, Paris, France [C. L. G.]

The effect of several well-characterized monoclonal anti-idiotypic antibodies on the in vivo growth of idiotype-bearing murine plasmacytoma cells was examined. They were chosen from a group of immunoglobulin G1 antibodies which react with the binding site determinants of M460, the immunoglobulin A dinitrophenyl-binding myeloma protein secreted by and present on the surface of MOPC-460, and included representatives of two families which recognize different determinants in the M460 variable region. The antibodies were administered daily, beginning 2 hr before i.v. tumor cell inoculation, and the effect on the appearance of tumor colony formation in the spleen was judged after 14 days. All four antibodies tested were inhibitory. At the highest doses used, the number of splenic tumor foci was reduced by up to 97%. The effect was highly specific since the growth of MOPC-315, which also produces an immunoglobulin A dinitrophenyl-binding myeloma protein, was unaffected by the antibodies, and a similarly prepared immunoglobulin G1 monoclonal antibody against an unrelated idiotype did not affect the growth of MOPC-460. The inhibition of tumor growth appears to be independent of complement and antibody-dependent cellular cytotoxicity mechanisms. A small fraction of clones escaping the antitumor effect of anti-idiotypic antibodies has stopped expressing the idiotype.

¹ This investigation was supported by the Italian National Research Council (C.N.R.) special projects "Control of Neoplastic Growth" and "Oncology."

² To whom requests for reprints should be addressed, at the Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Via Sergio Pansini 5, 80131 Napoli, Italy.

Received 6/20/84. Accepted 8/ 3/84.

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