The specific blocking of humoral immune cytolysis mediated by anti-tumor antibodies degraded by lysosomal enzymes of tumor origin.

Abstract

The IgG fraction from rabbit antisera against a mouse plasmacytoma (RaPCT-IgG) was incubated, under acidic conditions, with lysosomal extracts (LE) derived from the corresponding tumors. The LE-treated IgG demonstrated a significant decrease in its complement-dependent cytotoxic potential when compared to RaPCT-IgG incubated without LE under the same conditions (control IgG). Ammonium sulfate (AS) precipitation of the control IgG and the LE-treated IgG preparations at 40% saturation of AS revealed that some of the IgG lost its precipitability at this AS concentration after LE treatment, but could be precipitated at 60% or 70% saturation. The LE-treated IgG and control IgG fractions that precipitated by 40% saturated AS showed similar gel filtration profiles. The LE-treated IgG fraction precipitating at 70% saturation of AS (but not at 40%) showed a different gel filtration profile. This fraction was separated into several subfractions, some with an apparent lower molecular weight. Some of these subfractions which still contained antigenic IgG lacked any expression of antigenic Fc, and were not cytotoxic to tumor cells. They could, however, rebind to tumor cells and block the complement-dependent cytotoxic activity of native RaPCT-IgG. Lysosomal enzymes of tumor origin seem, therefore, to convert cytotoxic anti-tumor antibodies into molecules devoid of Fc but still retaining their antigen binding activity. Such an activity, if occurring in vivo might enhance tumor growth.