Regulation of tumor growth and antibody clone expression by antigen and anti-idiotype antibody ligands with specificity for receptor-binding sites.

Dextran ligands, modified to increase epitope reactivity with receptors, were more effective in suppressing BALB/c mouse plasmacytomas MOPC 104 E and J-558, which bind alpha (1 leads to 3) dextran and have an idiotype (Id) in the common, than autoantibody (Ab) against the Id unique to each of the proteins secreted by the two tumors (the (IdI). BALC/c immunized with 104 E myeloma protein and expressing an antibody response to the 104 E IdI exhibited a specific, anti-104 E IdI transplantation resistance to lethal grafts of 104 E, but not J-558, tumors notwithstanding the shared common Id and similar ability to bind alpha(1 leads to 3) dextran. This autoantibody did not prevent modulation of the 104 E tumor to variant forms or the growth of the variants. On challenge with alpha (1 leads to 3) dextran, the immunized mice expressing the anti-104 C IdI responses failed to express the 104 D IdI-like antibody clone present in the normal, anti-alpha (1 leads to 3) dextran antibody repertoire. Passive, iso-anti-104 E IdI antibody had a transitory suppressive effect on the normal, 104 E IdI-like antibody clone but failed to circumvent 104 E tumor growth. It is apparent that the greater effectiveness of ligands strongly reactive in a nonphysiological manner with the tumor receptors lies in the stabilization of the tumor load without inducing variant escape or a disturbance of the immune network, and that receptor expression and malignancy state are not necessarily co-extensive functions.