Protection Against a Syngeneic Mammary Adenocarcinoma by Administration of Idiotypic and Anti-Idiotypic Antibodies

A hybridoma secreting a monoclonal antibody (mAb) with specificity for tumor-associated cell surface antigens of a transplantable murine mammary adenocarcinoma (SMC-168) was prepared by fusion of syngeneic C3H/He spleen cells with SP2 myeloma cells. Mice which were pretreated with this mAb (C–73) were significantly resistant to the outgrowth of a tumorigenic dose of SMC-168 cells when compared to controls. The treated nice developed tumor-specific cell-mediated immunity, measured by leukocyte adherence inhibition (LAI), which was equal to that of mice immunized with live tumor cells. The IgG fraction from serum of mice receiving mAb C-73 contained antibodies which would bind to that mAb suggesting the presence of anti-idiotypic antibodies (anti-Id). This binding could be partially inhibited by a soluble l-butanol cell surface extract of SMC-168. Rabbits were immunized with mAb C-73 to produce a polyclonal anti-Id. The purified and absorbed IgG fraction of this serum would bind only to mAb C-73 and not to other mAbs of the same isotype or normal C3H/HeN IgG. Binding of the rabbit anti-Id to mAb C-73 could be partially inhibited by soluble tumor-associated antigen extracted from SMC-168. Mice immunized with this polyclonal anti-Id vaccine developed tumor-specific cell-mediated immunity and were significantly resistant to the outgrowth of a tumorigenic dose of SMC-168.