A synergistic effect between anti-idiotype antibodies and anti-neoplastic drugs in the therapy of a murine B-cell tumor.

Antibodies directed against idiotypic determinants of the cell-surface IgM of a B lymphoma, 38c, were effective in delaying development of the tumor and in some instances in preventing its growth. The efficacity of the anti-idiotype antibodies was markedly increased when they were injected in combination with anti-neoplastic drugs. Since chemotherapy, as such, is limited by the general toxicity of the drugs it was of advantage to apply them in low doses. The drug doses used were mostly ineffective by themselves, yet were active in combination with the antibody in a more than additive fashion. We performed studies designed to elucidate the mechanism of the synergy between the anti-idiotype antibodies and the drugs. The data suggest that the activity of the antibody is partly indirect and is mediated through the host's effector cells. In the case of one drug, daunomycin, the activity is also, at least in part, mediated through peritoneal exudate cells (PEC). Daunomycin injected intraperitoneally activated PEC. Such activated PEC, when injected into recipient mice, could replace the drug in its synergy with the antibody. In conclusion, it was shown that it is possible to increase the effectiveness either of antibodies to tumor cells or of cytotoxic drugs by combination therapy.